Background: an impossible mission?

Probably, we all have faced at least once the tremendous dilemma of “what to do” with a young, obese patient on dialysis. Should we convince him-her trying the 100^th diet? Should we desperately look for a transplant Center agreeing to wait-list our obese patient? Should we look for a bariatric surgeon, accepting to treat a dialysis patient, accepting the risks of rapid weight loss on dialysis, and, eventually, not to wait list our patient due to the frequent complications of invasive surgery? Or, more simply, should we smile, and pat on the shoulder, saying “dear, sure, we’ll have you waitlisted once you have lost weight”?

In the context of the global obesity epidemic, obesity is increasingly encountered in dialysis patients [1]. This is due to evolving epidemiological features in Western and developing Countries where obesity is a rising concern. Moreover, obesity is a major cause and/or it contributes to CKD by itself [2] [3] [4]. A recent systematic review underlined the importance of weight loss in slowing the progression of kidney diseases and underlined also how the best way form attaining weight loss is far from being defined [5].

The problem of obesity (and consequently weight loss) on dialysis has often been defined as a paradox [6] [7]. The dialysis population is at constant threat of malnutrition and protein energy malnutrition are strictly associated with mortality risks. Indeed, the survival of dialysis patients may be overall too short to demonstrate the risks linked to obesity and overweight [8] [9] [10].

This situation, considered an example of “reverse epidemiology”, is paradoxical not only from an epidemiological point of view but also from a clinical one [11]. Losing weight is required by several transplant Centers, in order to better manage the limited resources available. Indeed, it has been reported a survival advantage for obese transplanted patients compared to obese patients on dialysis. However, the best way to lose weight is far from being defined, and the most effective treatment for morbid obesity on dialysis, i.e. bariatric surgery, carries a specific risk of oxalate deposition after kidney graft [12] [13] (full text) [14] (full text) [15] (full text).

Furthermore, it is not clear how to treat obese patients that require dialysis. In fact, obesity is often considered a relative contraindication to peritoneal dialysis as it impairs dialysis efficiency, and may pose challenges in obtaining vascular access. Despite, at least theoretically, non-conventional dialysis schedules - such as daily or nightly dialysis - may have specific advantages, as far as we are aware no study combined the two issues of daily dialysis and weight loss in End Stage Renal Disease (ESRD) patients.

Since obesity is increasing worldwide, new therapeutic approaches are currently studied. For example, the use of qualitative “ad libitum diets” and “metabolic challenges”, to allow rapid weight loss alternated to maintenance phases [16] [17] (full text) [18].

In dialysis patients, hypercatabolic states, leading to hyperphosphatemia or hyperkalemia, are common threats that could increase during rapid weight loss. Thus, testing the combination of intensive dialysis and intensive weight loss will open new perspectives for our patients.

Aim of the present case report is to describe a patient who attained a remarkable weight loss (-18.5 Kg, -6.3 Kg/m² BMI) by the combination of daily dialysis and a coach-assisted, personalised and intensive weight loss program. Therefore, this case may suggest a tailored and intensive dialysis approach to young and motivated obese dialysis patients, which primary therapeutic goal should be transplantation.

The case

In this report we describe a 56 year old male patient on dialysis since February 2011.

The patient was overweight since the adolescence, except for a period between 20 and 35 years of age, when he lost weight by physical exercise and a careful self-made diet, reaching the weight nadir (75 Kg, BMI 25.9 Kg/m²). Therefore, he gradually and progressively regained weight up to a maximum of 110.5 Kg (BMI 37.7 Kg/m²).

In 1978 the patient underwent a kidney biopsy confirming a diagnosis of acute glomerulonephritis. No therapy was done and the renal function remained stable until 2000, when the patient developed nephrotic proteinuria (6-11 g/day), thus leading to a second kidney biopsy resulting in a diagnosis of focal segmental glomerulosclerosis (FSGS).

The patient underwent 6 months steroid and immunosuppressive therapy with partial response (Proteinuria: 3-4 g/day). Two years later, he was treated with ACE-inhibitor and angiotensin-receptor-blockers because of persistent nephrotic proteinuria. However, in spite of all efforts, his renal function gradually worsened.

Nowadays, no available data allow defining the disease as strictly obesity related. However, the hypothesis that obesity played a role in the pathogenesis and/or in the progression of the disease may be supported by the relatively slow clinical course, the lack of a significant response to steroid treatment and the lack of any other signs of immunological activity.

The patient was referred to our Unit in 2009, with creatinine 3.4 mg/dL and proteinuria 8 g/die. He started a vegan supplemented low protein diet, which he followed for about one year with good compliance, until the start of dialysis.

The dialysis schedule

Ten months before the start of the diet the patient started dialysis with an incremental policy, 2 to 6 sessions per week, due to the rapid loss of residual kidney function, that probably occurred quite rapidly also because of two surgical interventions for bilateral knee prosthesis.

Before starting the diet the patient was on a daily dialysis schedule with the Nxstage system with Kt/V 0.56 per session, corresponding to EKRc 16 mL/min according to the EKR model, developed by Casino and co-workers [19] (full text). Subsequently, at the beginning of the diet, the patient was switched to conventional bicarbonate dialysis with a daily schedule, for better adapting the dialysis prescription to the eventual metabolic derangements and to patient’s needs.

Dialysis frequency was already high since the beginning, but duration of dialysis sessions needed to be adapted, for an average of 2-3 hours per session, based on the necessity to increase ultrafiltration, in particular during the phases of rapid weight loss. The dialysis efficiency remained good throughout the whole period of follow up, with a Kt/V ranging between 0.68-0.79; EKRc 17-20 mL/min.

Biochemical controls (including blood cell count, blood urea nitrogen, sodium, potassium, acid-base balance, total calcium, phosphate, intact parathyroid hormone, serum albumin) were scheduled weekly, during rapid weight loss phase, and monthly thereafter, in order to restore the usual rate of controls for dialysis patients at our Unit.

The diet

The diet was made available as a pilot feasibility study of a weight reduction program in the context of flexible dialysis.

The diet plan (Coaching Biomis) belongs to the “new generation” of qualitative, ad libitum diets [17] (full text). In analogy with other pattern of nutritional intervention, including the Mayo Clinic diet, the main goals are weight-loss and educational programs [16] [18]. Also, based on some recent literature suggestions, it is coach-assisted in order to improve patient compliance [20] (full text). Moreover, in analogy with the Mayo Clinic diet, it is divided into two phases: “rapid weight loss”- during which the patient is allowed to eat one different food at each meal, in liberal quantities - and a “maintenance” phase - where the patient combines different foods into an overall “Mediterranean” pattern. The patient needs to measure daily body weight, blood pressure and some anthropometric measures (neck, thorax, waist, hips, thigh, ankle circumferences) and to report them to the coach. At the same time, the patient receives a 2 day (rapid weight loss) or a 7 day (maintenance) diet program, consisting of liberal quantities of three or more different foods, chosen on the basis of their biochemical profile and lower glycaemic index. This choice does not take into consideration the caloric intake, that is not monitored. The diet is salt, alcohol and sugar free while extra virgin olive oil and spices are permitted in liberal quantity. Nuts are allowed in the maintenance phase and a lemon-based snack is allowed in the morning.

Follow-up and results

The patient underwent two diet periods consisting of a rapid weight loss (7 and 5 months respectively) and a maintenance phase. Between the first and the second period of diet, the patient discontinued the program for personal reasons for about 5 months. The overall follow up lasted 21 months.

The results of the rapid weight loss phases were good and the patient self reported a very good compliance to the diet; conversely, in particular during the first maintenance phase, he partially regained the lost weight and he found the diet exceedingly difficult to follow. However, after resuming the diet, he reported a better adaptation to the diet protocol, leading to a slow and progressive further weight loss, in keeping with long term results of the educational program.

Figures (Figura 1, Figura 2 e Figura 3) report weight loss and BMI throughout the whole diet period and the main anthropometric measures.

At the end of 21 months of follow up the weight loss was 18.5 Kg; delta BMI -6.3 Kg/m²; 50% of total overweight loss, calculated considering the weight at which BMI is 25; reduction in waist-to hip ratio 1.18 to 1.06: -0.12; reduction in waist circumference -16 cm.

Interestingly, in spite of the impressive weight loss, the main indexes of nutritional status, as albumin, total proteins and haemoglobin, remained good and stable during the whole period of follow up: albumin 3.5-3.8 g/dL; total serum proteins 7-7.4 g/dL; haemoglobin 11.4-12.1 g/dL.

Lipid profile at the end of follow up was normal (total cholesterol 142 mg/dL; HDL-cholesterol 40 mg/dL; triglycerides 62 mg/dL), as well as glycosylated haemoglobin (36 mmol/mol) and TSH (1.13 mcIU/mL).

The bio-impedance test, performed with BCM Fresenius [21] at the end of the follow up, showed a well-preserved lean mass; particularly, both LTI (Lean Tissue Index: weight/height²) and LTM (Lean Tissue Mass) index were normal for the referring population (respectively 14.9 Kg/m² and 43.2 Kg, equivalent to 46.4% of the whole body mass).

Furthermore, the calcium balance remarkably improved, allowing reduction of phosphate binders (Lanthanum carbonate 1500 mg/day to 750 mg/day, Sevelamer 1.6 g/day to 0.8 g/day, discontinuation of calcium carbonate); meanwhile, cinacalcet was increased (30 mg/day to 60 mg/day). Iron supplementation was reduced (125 mg/week to 62.5 mg/week) as well as erythropoietin dose (darbepoetin alpha 40 mcg/week to 40 mcg/2 weeks); anti-hypertensive therapy and oral citrate were discontinued. Trend of the main clinical test performed during the different periods of diet are reported on Tabella 1.

Side effects

No severe side effects were recorded; however, the patient experienced - immediately after the start of the diet - a sudden drop in blood pressure, with normal BNP and cardiac ejection fraction, leading to discontinuation of Amlodipine and to an increase of Na content in the dialysate (138 to 142 mEq/L). He also complained of teeth discoloration, presumably due to an effect of the lemon-based snacks on teeth enamel. 

Discussion

Our interest for the case here reported mainly resides in the combination of two relatively new approaches: daily dialysis with flexible schedules and a rapid weight loss program.

Rapid weight loss is a great challenge for dialysis patients. The main concerns regard both the risk of protein malnutrition, further reducing the already diminished muscle mass in uremic patients, and hypercatabolism, (e.g. increase in potassium and phosphate levels), directly related to acute muscle mass loss. On these bases, some Authors suggest to be very careful in using weight reducing programs in dialysis patients. Moreover, they introduce weight and BMI as a muscle mass surrogate (measured by handgrip and bio-impedance tests) [22] [23] (full text). In such a context, an increased potassium level, worsening metabolic acidosis as well as altered calcium-phosphate balance are to be expected.

Quite surprisingly, none of the feared side effects was recorded in our patient, who, on the contrary, displayed a surprising improvement in Ca-P-PTHi balance and an improved acidosis correction. Interestingly, this was not due to the modest increase in dialysis time, as the EKRc remained quite stable over time. The improvement in Ca-P-PTHi balance is difficult to explain. We think that “healthier” food habits may have been played a role (no canned food, or commercial snacks) by reducing a quota of phosphate rich additives, whose contribution to hyperphosphatemia in CKD and dialysis patients has only recently been recognised as very important [24] (full text).

Moreover, at the beginning of the diet the patient was neither oedematous nor severely hypertensive: hence, the weight loss attained was not merely a reflection of a new balance - as often found at the start of dialysis, when patients loose mainly the hyperhydration quota, as soon as the dialysis balance is reached. Importantly, we need to focus on the blood pressure drop, recorded shortly after the diet was started. In fact, we think that an increase of Na content in the dialysate in order to correct hypotension, in spite of normal blood sodium levels, was associated to the very low- sodium diet. However, the major effector of the low sodium diet is usually considered to be the kidney and our patient was anuric. This observation, deserving further attention, may underline the importance of the direct effect of sodium content on systemic vasculature, as suggested by some authors thus leading to reconsider the importance of low sodium diets in hypertensive dialysis patients.

Indeed, being wait listed for transplantation was the main motivation for starting the diet program, choosing a schedule of rapid weight loss and following it with some difficulties but with strong determination. Such a consideration further underlines the need for a motivational approach, not only to weight loss, but to the overall diet in dialysis patients. Also it suggests that the particular situation of our Unit (the head nurse having been the first person to experience the tested diet and the promoter of sharing this experience with our patients) may have create a particularly favourable context. In this scenario, it is impossible to distinguish the effects of the dialysis schedule, from diet and clinical and relational context. A larger study about the feasibility of such a dietary intervention in obese dialysis patients is needed, ideally on a multicentre basis.

Conclusions (personal and general conclusions)

We are well aware that this is only a pilot experience with one single, motivated, “difficult” patient and that no universal law can be written on a single case. However, there are some issues in his story that positively surprised us, and that we wished to share in this report: as we mentioned in the introduction, we felt that weight loss in our patient was a “mission impossible”. Jet, as he wanted to try a completely new qualitative approach, and he was willing to further increase dialysis, we did not see any a priori contraindication to this trial. Being the first one to test a treatment often means being highly motivated, and the results were positive in term of compliance. Moreover, possibly because of the “ad libitum” approach, and due to the personalised schema, he succeeded in loosing weight without impoverishing the lean body mass, as also witnessed by the good potassium and phosphate controls. Hence, overall our experience suggest that rapid weight loss programs may be applied also to hemodialysis patients.

Obese patients are a living demonstration that one size doesn’t fit all; a flexible approach may be a clue in this context.

We acknowledge our bias of passion for daily hemodialysis [25] [26]; however we are convinced that the key of success and, most importantly the lack of severe side effects resides in a combination of a strong patient motivation, a strict control schedule and a “higher than usual” dialysis efficiency.