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innovations in treatment bmj case rep first published as 10 1136 bcr 2019 232080 on 23 december 2019 downloaded from case report plant based dietary approach to stage 3 chronic ...

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                                                                                                                                                     Innovations in treatment                               BMJ Case Rep: first published as 10.1136/bcr-2019-232080 on 23 December 2019. Downloaded from 
                                                    Case report
                                                    Plant- based dietary approach to stage 3 chronic 
                                                    kidney disease with hyperphosphataemia
                                                                                              1                            2
                                                    Thomas M Campbell      ,  Scott E Liebman  
               1Family Medicine, University         SUMMARY                                                                   case highlights the potentially remarkable benefit 
               of Rochester Medical Center,         A 69-       -                                   , hypertension            that a strict WFPBD may offer, particularly when 
                                                           year old man with type 2 diabetes
               Rochester, New York, USA             and stage 3 chronic kidney disease (CKD),                                 used in the context of advanced metabolic disease 
               2Nephrology, University of           hyperphosphataemia and borderline hyperkalaemia                           and CKD.
               Rochester Medical Center,            presented to an office visit interested in changing his diet 
               Rochester, New York, USA             to improve his medical conditions. He adopted a strict 
                                                    whole- foods, plant- based diet, without calorie or portion               CASe pReSenTATion
               Correspondence to                    restriction or mandated exercise, and rapidly reduced his                 A 69- year-old man         presented for advice regarding 
               Dr Thomas M Campbell;                                                                                          diet and lifestyle approaches to treat his chronic 
                thomas_ campbell@ urmc.             insulin requirements by >50%, and subsequently saw                        medical problems. His medical history included 
               rochester. edu                       improvements in weight, blood pressure and cholesterol.                   stage 3 CKD, class 2 obesity, hypertension, hyper-
                                                    His estimated glomerular filtration rate (eGFR) increased                 lipidaemia and type 2 diabetes requiring approxi-
               Accepted 11 December 2019            from 45 to 74 mL/min after 4.5 months on the diet                         mately 210 total units of insulin daily (140 units 
                                                    and his microalbumin/creatinine ratio decreased from                      insulin glargine and approximately 20–25 units 
                                                    414.3 to 26.8 mg/g. His phosphorus level returned to                      insulin lispro at three meals daily).
                                                    the normal range. For individuals with CKD, especially                       He was most concerned about the general wors-
                                                    those with obesity, hypertension, or diabetes, a strict,                  ening of his numerous chronic medical conditions. 
                                                    ad libitum whole- food, plant- based diet may confer                      His diabetes had been diagnosed roughly 30 years 
                                                    significant benefit, although one must consider potential                 ago and he had progressed to requiring insulin 
                                                    limitations of a creatinine- based GFR equation in the                    about 4–5 years prior to our visit. His diabetes 
                                                    face of significant weight loss.                                          was only marginally controlled (haemoglobin A1c 
                                                                                                                              7.3%) despite steady escalation of insulin dosing 
                                                                                                                              and significant diet and lifestyle efforts. He was on 
                                                                                                                              12 different medications (box
                                                    BACkgRoUnd                                                                                                           1) and had experi-
                                                    Approximately one in seven American adults have                           enced troublesome side effects, particularly weight 
                                                    chronic kidney disease (CKD) and the prevalence                           gain. His ‘tipping point’ was his recent diagnosis of                          http://casereports.bmj.com/
                                                    is higher in those with metabolic risk factors such                       hyperphosphataemia (phosphorus 4.8 mg/dL) and a 
                                                                                             1                                conversation with his nephrologist in which he was 
                                                    as hypertension and diabetes.  Obesity is an inde-
                                                                                                                      2 3     told that he might progress to the need for dialysis 
                                                    pendent, causative factor in CKD pathogenesis.
                                                    People with CKD have significantly higher risks of                        in as soon as 5 years.
                                                    cardiovascular disease (CVD) than those without                              He was married with a supportive wife who did 
                                                            4                                                                 the shopping and cooking. He was a retired busi-
                                                    CKD.                                                                      ness executive who continued to work part time 
                                                       Given that nutrition plays an important role in                        on rental properties he owned. He was a former 
                                                    metabolic health, some kidney-related               organisations         smoker (quit almost 20 years prior to visit), drank 
                                                    advise dietary approaches for CKD addressing these 
                                                                     5 6 including the Dietary Approaches  2–3 alcoholic drinks weekly and denied illicit drug                                                on January 3, 2023 by guest. Protected by copyright.
                                                    risk factors,                                                             use. Foods and meals typical of his baseline diet 
                                                    to Stop Hypertension (DASH) diet, as it leads to                          included: a breakfast of shredded wheat, coffee, 
                                                    weight loss, reduced blood pressure and improved 
                                                    glycaemic control in different populations.7 The  lunch of macaroni with meat sauce or grilled cheese 
                                                    dietary recommendations in the Kidney Disease  sandwich, dinner of Italian wedding soup (with 
                                                    Improving Global Outcomes focus on protein and                            meatballs) and beans and rice. Beverages consisted 
                                                    salt intake and education with attention to potas-                        of coffee, water and an occasional alcoholic drink. 
                                                    sium, salt, phosphate and protein intake, but do  He and his wife dined out once a week. He often 
               © BMJ Publishing Group               not make specific recommendation as to dietary  had an evening snack of cookies or peanut butter 
               Limited 2019. Re- use                                                   8                                      cheese crackers. He walked 45 min a day on his 
               permitted under CC BY- NC. No        patterns or specific foods.                                               indoor treadmill.
               commercial re- use. See rights          A more stringent whole- foods, plant- based diet 
               and permissions. Published           (WFPBD) has been shown, over a variety of trials, to 
                                                                                                            9–11 hyper-
               by BMJ.                              successfully treat coronary artery disease,                               inveSTigATionS
                                                               12 13           14                    15 16
                 To cite: Campbell TM,              tension,         obesity  and diabetes.                 Thus it is        His laboratory values from approximately 6 weeks 
                 Liebman SE. BMJ Case               possible that a more stringent nutritional approach                       prior to his office visit are shown in the first 
                 Rep 2019;12:e232080.               may yield significant benefit in patients with CKD.                       column of table 1. The estimated glomerular filtra-
                 doi:10.1136/bcr-2019-              Unfortunately, there is limited intervention research                     tion rate (eGFR) was calculated by the Chronic 
                 232080                             on the effects of this dietary pattern on CKD. This                       Kidney Disease Epidemiology (CKD- EPI) equation, 
                                                          Campbell TM, Liebman SE. BMJ Case Rep 2019;12:e232080. doi:10.1136/bcr-2019-232080
                                                                                                                                                                                                  1
                      innovations in treatment                                                                                                                                                                                                                                     BMJ Case Rep: first published as 10.1136/bcr-2019-232080 on 23 December 2019. Downloaded from 
                       Box 1  Baseline medications                                                                                                beans) cooked in vegetable stock, dinner of whole-wheat  
                                                                                                                                                  spaghetti and steamed veggies, all cooked and prepared without 
                       Amlodipine 2.5 mg daily.                                                                                                   oil, and at least two fresh clementines as snacks.
                       Aspirin 81 mg daily.                                                                                                            Due to the rapid effect of major dietary change on insulin 
                       Carvedilol 25 mg two times per day.                                                                                        sensitivity, immediate adjustments in insulin dosing were made 
                       Hydrochlorothiazide 12.5 mg daily.                                                                                         and the patient was called daily after starting the diet to assess 
                       Losartan 100 mg daily.                                                                                                     blood sugars and further decrease insulin as necessary.
                       Pravastatin 40 mg daily.
                       Insulin glargine 140 units nightly.                                                                                        oUTCoMe And Follow-Up
                       Insulin lispro 20–25 units three times per day before meals.                                                               The patient and his wife reported being highly compliant. They 
                       Glimepiride 4 mg daily.                                                                                                    admitted to one meal a week at a restaurant when they were 
                       Sitagliptin 100 mg daily.                                                                                                  not 100% compliant, but otherwise followed the food guide 
                       Fish oil 1000 mg daily.                                                                                                    strictly. Within 4 days, insulin had been reduced from roughly 
                       Vitamin D 2000 IU daily.                                                                                                   210 to 70 units daily and glimepiride was stopped due to rapidly 
                       Continuous positive airway pressure device at night.                                                                       improving blood sugar. After his blood sugar stabilised his insulin 
                                                                                                                                                  was titrated up slightly to about 80 units a day by the end of his 
                    incorporating age, serum creatinine, sex and race as independent                                                              second week on the diet to achieve tighter glucose control.
                                      17                                                                                                               He stopped carvedilol, hydrochlorothiazide, amlodipine and 
                    variables.                                                                                                                    sitagliptin within the first 2 months due to improving blood 
                    TReATMenT                                                                                                                     pressure and blood glucose. His insulin was steadily titrated 
                    The patient and his wife were given a food guide detailing what                                                               downward. His pravastatin dose was cut in half and he had a 
                    groups of food were appropriate for a WFPBD (table 2). He was                                                                 follow- up visit with nephrology about 4.5 months into the 
                    counselled to eat whenever hungry and as much as needed to                                                                    dietary change, at which point he had lost roughly 22.2 kg. 
                    be comfortably full without counting calories, carbohydrates, or                                                              Due to marginal hyperkalaemia (potassium of 5.3 mmol/L) and 
                    restricting portion sizes. He was provided with a shopping list                                                               improvements in weight, blood pressure and creatinine, his 
                    consisting of common products in area grocery stores consistent                                                               nephrologist halved his losartan dose, from 100 mg to 50 mg 
                    with the food guide and a restaurant guide to facilitate compli-                                                              daily. His insulin dose had dropped to 46 units daily total within 
                    ance with the diet while eating out. He also received a book with                                                             5 months. His remaining medications after 20 weeks of dietary 
                    over 50 whole- food, plant- based recipes and ‘how-to’ instruc                                                      -         change are shown in box 2.
                    tions for implementing the diet. He was asked to start a vitamin                                                                   His renal function, as measured by creatinine and eGFR, 
                    B12 supplement.                                                                                                               showed slight improvement within 2 months, and significant 
                         The comprehensive counselling and behavioural intervention                                                               improvement 4.5 months after changing his diet (figure 1). His 
                    took over 1 hour and both the patient and his wife participated.                                                              creatinine was in the normal range for the first time in at least 8 
                    They decided to start the dietary programme 3 days after the                                                                  years (the duration of available laboratory tests in the electronic 
                    office visit.                                                                                                                 medical record). His microalbuminuria resolved, at least tempo-                                                                  http://casereports.bmj.com/
                         An example day on this plan included breakfast of oatmeal                                                                rarily, but then increased thereafter. His metabolic acidosis 
                    with fruit and flaxseed, lunch of beans and kale (greens and                                                                  resolved. Selected laboratory results are shown in table 1.
                      Table 1  Selected laboratory values and weight before and after dietary therapy
                                                                              17 February                                                                                                                                                            15 March 
                                                                              2017                      9 April 2017                      18 April 2017                  3 May 2017                1 June 2017             24 August 2017 2018
                      Potassium (mmol/L)                                         4.6                    Started diet                        5                                4.5                       4.7                    5.3                       5.1
                      CO (mmol/L)                                               21                                                        24                               23                        22                      25                       25                            on January 3, 2023 by guest. Protected by copyright.
                          2
                      Urea nitrogen (mg/dL)                                     39                                                        32                               22                        23                      19                       21
                      Creatinine (mg/dL)                                         1.56                                                      1.67                              1.45                      1.44                   1.03                      0.98
                                                    2
                      eGFR (mL/min/1.73 m )                                     45                                                        41                               49                        49                      74                       78
                      Phosphorus (mg/dL)                                         4.8                                                       4.4                               3.9                       4.7                    4.1                       4.1
                      Albumin (g/dL)                                             4.3                                                                                                                   4.1                    4.3                       4.7
                      Total cholesterol (mg/dL)                               181                                                                                                                  118                     110                       148
                      Triglycerides (mg/dL)                                   148                                                                                                                  123                     103                        84
                      HDL cholesterol (mg/dL)                                   48                                                                                                                   37                      44                       50
                      LDL cholesterol (mg/dL)                                 103                                                                                                                    56                      45                       81
                      Chol/HDL ratio                                             3.8                                                                                                                   3.2                    2.5                       3.0
                      Haemoglobin A1c (%)                                        7.3                                                                                                                   6.8                    6.1                       6.0
                      Creatinine, UR (mg/dL)                                    89                                                                                                                   60                      28                       75
                      Microalbumin, UR (mg/dL)                                  36.87                                                                                                                  1.61                   2.71                    11.56
                      Microalb/creat ratio                                    414.3                                                                                                                  26.8                    96.8                    154.1
                      Weight (kg)                                                                       109.4                                                            102.8                       94.8                    87.1                     78.5
                                     2
                      BMI (kg/m )                                                                       39.5                                                               37.1                      34.3                    31.5                      28.4
                      BMI, body mass index; eGFR, estimated glomerular filtration rate; HDL, high-density lipoprotein;                          LDL, low- density lipoprotein.
                                                                                                                                        Campbell TM, Liebman SE. BMJ Case Rep 2019;12:e232080. doi:10.1136/bcr-2019-232080
                    2
                                                                                                                                                              innovations in treatment                                   BMJ Case Rep: first published as 10.1136/bcr-2019-232080 on 23 December 2019. Downloaded from 
                  Table 2  Food guide
                  ‘Allowed’ foods                                              Foods to avoid                                                     Foods to enjoy sparingly
                  Non- starchy  vegetables                                     Meat (including fish and poultry)                                  Unsalted, raw or dry roasted nuts, natural nut butters
                  Starchy vegetables (potatoes and beans)                      Dairy foods                                                        Avocadoes
                  Whole grains, including whole grain flours                   Added pure fats (all oils, butter, margarine)                      Coconut
                  Fresh fruit (not dried, no juices or smoothies)              Eggs                                                               Seeds
                  All spices                                                   Vegan ‘replacement’ foods—fake meats, fake cheeses                 Dried fruit
                  Ground flaxseed and chia seed                                Refined flours                                                     Added sweeteners (maple syrup, fruit juice concentrate, 
                                                                                                                                                  added sugars)
                  Water, non- dairy plant-‘milks’, tea                         Predominantly ‘added sugar’ foods (candy, snack/energy             Coffee, alcohol
                                                                               bars, cookies, cakes, pastries)
                                                                               Soda, fruit juice, sports drinks, energy drinks, blended coffee    Refined soy protein and wheat protein (tofu, seitan)
                                                                               and tea drinks
                    His hyperphosphataemia improved on a WFPBD, without                                            reduced blood pressure, improved the acidosis and slowed 
                                                                                                                                                                                                             22
                adjustment for phosphorus intake and his potassium, which had                                      eGFR declines over 3 years compared with control patients.  
                been on the high end of the normal laboratory range, remained                                      More recently Kim et al analysed data from the Atheroscle-
                there or marginally above the normal range. He was advised                                         rosis Risk in Communities study and found higher adherence 
                continued adherence to the food guide, but to choose lower                                         to a healthy plant based diet correlated with a decrease rate of 
                potassium plant- based foods.                                                                      incident CKD.23 Apart from kidney-specific outcomes, overall                                  
                    The patient and his spouse remained compliant and results                                      mortality is significantly lower among individuals with eGFR 
                from approximately 11 months after starting the diet showed                                        <60 mL/min who consume higher ratio of plant to animal 
                persistent benefit, although his microalbuminuria increased after                                  protein.24 25 This last point deserves emphasis as individuals 
                a nadir 4 months after changing his diet.                                                          with CKD of any stage are more likely to die prematurely 
                                                                                                                   than progress to dialysis,26 with CVD being the most common 
                                                                                                                                          27
                                                                                                                   cause of death.  Given the benefits of a WFPBD in CVD in 
                diSCUSSion                                                                                                    9–11
                This case illustrates an alternative treatment approach that may                                   general          it is feasible they exert a similar effect in CKD 
                be appropriate for select, highly motivated patients, using a strict                               patients, who are already at increased CVD risk.
                WFPBD. This approach may offer effective treatment of CKD in                                           Phosphorus and potassium are often a concern in CKD 
                patients with the common metabolic comorbidities of obesity,                                       patients. Plant- based diets may offer benefit for hyperphospha-
                                                                                                                   taemia as phosphorus is not as efficiently absorbed from plant 
                hypertension and diabetes.                                                                         sources.28 Moe et al demonstrated this in a randomised crossover 
                    Previous studies offer support for this approach, though to                                    trial examining nine patients randomised to alternate between 
                our knowledge few controlled diet or lifestyle intervention                                        an animal-protein-           heavy diet or a plant-protein-              heavy- diet for 
                have shown improvement of kidney function to the degree                                            two separate 7-day period separated by a                         2–4-week        washout              http://casereports.bmj.com/
                found in this case. Goldner described two patients with lupus                                      period. Despite the diets having a similar phosphorous content, 
                nephritis who improved dramatically after adoption of a raw                                        patients’ phosphorus values were significantly lower after the 
                vegan nutrition protocol.18 Banerjee et al found that among                                        high plant- protein diet compared with the high animal- protein 
                American adults with CKD, those with the highest dietary                                           diet.29 Potassium is plentiful in plant- based diets, and the risk of 
                acid load (DAL) (associated with increased meat and cheese                                         hyperkalaemia requires specific dietary counselling on a case by 
                                                                                        19
                intake and reduced fruit and vegetable intake),  had signifi-                                      case basis, although a small pilot study investigating the effects of 
                cantly higher risk of progressing to end stage renal disease                                       2 weeks of a DASH diet in subjects with stage 3 CKD did not find 
                (relative hazard of 3.04 for highest tertile of DAL compared                                       any increased risk of hyperkalaemia with the higher potassium 
                                                           20                                                                       30
                with lowest tertile of DAL).  A prospective cohort study by                                        DASH diet.
                                  21                                                                                                                                                                                      on January 3, 2023 by guest. Protected by copyright.
                Khatri et al  found increasing adherence to the Mediterra-                                             Weight loss alone has significant impact on labs related to 
                nean diet among New Yorkers was associated with reduced                                            kidney function. Whether through bariatric surgery or pharma-
                risk of incident eGFR <60 mL/min. Similarly, a randomised                                          ceutical intervention, weight loss has been shown to improve 
                controlled trial found that adding fruits and vegetables to the                                    GFR and reduce albuminuria in several studies.31 32 Yet there are 
                diet of individuals with stage 3 CKD and metabolic acidosis 
                  Box 2  Follow- up medications 30 August 2017
                  Aspirin 81 mg daily.
                  Losartan 50 mg daily.
                  Pravastatin 20 mg daily.
                  Insulin glargine 28 units nightly.
                  Insulin lispro 6 units three times per day before meals.
                  Fish oil 1000 mg daily.
                  Vitamin D 2000 IU daily.
                  Continuous positive airway pressure device at night.                                             Figure 1  Changes in eGFR and creatinine from 2013 to 2018. eGFR, 
                  Vitamin B12 1000 µg daily.                                                                       estimated glomerular filtration rate.
                Campbell TM, Liebman SE. BMJ Case Rep 2019;12:e232080. doi:10.1136/bcr-2019-232080
                                                                                                                                                                                                              3
                  innovations in treatment                                                                                                                                                                               BMJ Case Rep: first published as 10.1136/bcr-2019-232080 on 23 December 2019. Downloaded from 
                inaccuracies in evaluating kidney function in the face of signif-                                  Twitter Thomas M Campbell @DrTomCampbell
                icant weight loss using creatinine-based                   eGFR formulas such as                   Contributors  TMC conducted all clinical care and wrote the original draft of the 
                the CKD-EPI          formula. The amount of lean body mass is signifi-                             manuscript. SEL edited and revised the manuscript.
                                                                                                          33
                cantly, positively associated with serum and urinary creatinine                                    Funding  The authors have not declared a specific grant for this research from any 
                and significant weight loss is accompanied by lean body mass                                       funding agency in the public, commercial or not- for- profit sectors.
                loss. Approximately 25% of total body weight lost, on average,                                     Competing interests  TMC receives royalties from general interest books 
                may be lost from fat free mass, though this proportion is highly                                   published about nutrition and health. He also has received honoraria and travel 
                variable and dependent on many factors.34 Thus, serum creati-                                      reimbursement for general interest lectures on the topic of plant- based nutrition and 
                nine may not be a reliable marker of kidney function in the face                                   health. He has received research support from the Highland Hospital Foundation, 
                of significant weight loss.                                                                        which has received donations from the T Colin Campbell Center for Nutrition Studies, 
                                                                                                                   the Thomas Hormel Foundation and numerous individuals.
                    In this case, while the patient dramatically improved his                                      patient consent for publication  Obtained.
                health in obvious, measurable ways, it is not possible to quan-                                    provenance and peer review  Not commissioned; externally peer reviewed.
                tify exactly how much his kidney function changed given his 
                significant weight loss (22.2 kg in the first 4.5 months). Body                                    open access  This is an open access article distributed in accordance with the 
                composition was not measured in this case. One study of                                            Creative Commons Attribution Non Commercial (CC BY- NC 4.0) license, which 
                bariatric surgery patients without CKD found that creatinine-                                      permits others to distribute, remix, adapt, build upon this work non- commercially, 
                                                                                                                   and license their derivative works on different terms, provided the original work 
                based eGFR increased by 12%–15% with an average weight                                             is properly cited and the use is non- commercial. See: http:// creativecommons. org/ 
                loss of 27 kg, while measured GFR did not change.35 In the                                         licenses/ by- nc/ 4. 0/.
                case presented here there was an increase in eGFR of 73%,                                          oRCid id
                suggesting that the improvement in estimated kidney function                                       Thomas M Campbell http:// orcid. org/ 0000- 0003- 4449- 8229
                was greater than what would be expected from weight loss 
                alone.
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                                                                                                           Campbell TM, Liebman SE. BMJ Case Rep 2019;12:e232080. doi:10.1136/bcr-2019-232080
                4
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...Innovations in treatment bmj case rep first published as bcr on december downloaded from report plant based dietary approach to stage chronic kidney disease with hyperphosphataemia thomas m campbell scott e liebman family medicine university summary highlights the potentially remarkable benefit of rochester medical center a hypertension that strict wfpbd may offer particularly when year old man type diabetes new york usa and ckd used context advanced metabolic nephrology borderline hyperkalaemia presented an office visit interested changing his diet improve conditions he adopted whole foods without calorie or portion presentation correspondence restriction mandated exercise rapidly reduced for advice regarding dr lifestyle approaches treat urmc insulin requirements by subsequently saw problems history included edu improvements weight blood pressure cholesterol class obesity hyper estimated glomerular filtration rate egfr increased lipidaemia requiring approxi accepted ml min after mont...

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