Cyclic VLCKD Meal Replacement in a Patient with Obesity and Mild Chronic Kidney Disease following Kidney Transplantation

Abstract

(1) Background: this work reports the clinical case of a man who underwent a kidney transplant at the age of 19 for idiopathic interstitial nephritis resulting in renal failure. (2) Methods: the patient also had severe obesity and underwent four cycles of a very low-calorie ketogenic diet (VLCKD) for weight loss. (3) Results: the cycles of diet therapy carried out during a six-year period allowed a significant weight loss (from 103.2 kg in 2012 to 87.5 kg in 2018) with lean mass conservation (from 49.9 kg to 52.5 kg) and a reduction of fat mass (from 53.3 kg to 35.0 kg), as assessed with bioimpedance analysis. Throughout the diet cycles, body weight remained stable, except for a weight regain that occurred between the 2nd and 3rd cycle. Renal function was preserved despite the known mild chronic kidney disease (creatininemia ranged from 1.11 mg/dL to 1.27 mg/dL, and GRF from 91 to 71 mL/min/1.73 m²). (4) Conclusions: this report shows that a VLCKD, performed under strict medical supervision, is safe and effective even in a complex clinical picture.

1. Introduction

In the last decades, obesity has become an increasing international public health issue affecting quality of life, increasing the risk of chronic non-communicable disease, and healthcare costs [1]. Management includes dietary interventions, lifestyle modifications, with a limited sedentary lifestyle and increased physical activity, preferably daily and aerobic, together with weight management drugs such as orlistat, naltrexone/bupropion and liraglutide. Furthermore, surgical therapy (gastric banding, sleeve gastrectomy, and Roux-en-Y gastric bypass) is available, significantly improving health and reducing mortality in patients affected by severe obesity [2]. Regarding the dietary approaches, the Mediterranean diet appeared to have positive effects on body weight and insulin resistance parameters [3], while for low glycemic index or glycemic load diets, the evidence is not yet sufficiently strong. In the context of obesity management, an emerging treatment is represented by very low-calorie ketogenic diets (VLCKDs) which, providing fewer than 800 kcal/day, allow rapid weight loss with a reduction in fat mass and with no substantial effect on lean body mass. Nevertheless, weight loss after one year or more of follow-up is comparable or superior to that achieved by other approaches [4]. Various programs aimed at weight loss, such as meal replacements, are commercially available, and their clinical use has increased significantly in the last years [5]. However, the scientific evidence of the safety and effectiveness of these approaches in patients suffering from obesity along with other comorbidities remains very limited.

The aim of the present work is to present the clinical case of a 37-year-old male patient suffering from severe obesity who underwent a kidney transplant at the age of 19, who successfully carried out cyclic VLCKDs for weight loss.

2. Materials and Methods

A male subject affected by idiopathic interstitial nephritis underwent a kidney transplant in 2004.

2.1. Clinical History

In 1995, the patient was diagnosed with chronic renal failure, following idiopathic interstitial nephritis. From 2002 to 2004, he underwent dialysis, firstly peritoneal and then extracorporeal. In 2004, he underwent a renal transplant from a deceased donor, with a good post-operative course. During childhood, the patient reported being mildly overweight, followed by a weight gain, especially during adolescence. A further weight gain occurred after renal transplantation in 2004, probably related to the intake of corticosteroid therapy for 3 years, which is the reason why he was prescribed a diet of about 1200 kcal/day by nephrologists, with no clinical benefit. The weight reached his plateau in January 2009, when he underwent the first examination at the Obesity Center of an Italian hospital. The patient’s home treatment included: cyclosporine 100 mg twice a day, mycophenolate mofetil 750 mg twice a day, ramipril 2.5 mg twice a day, amlodipine 5 mg 1 tb a day, esomeprazole 20 mg 1 tb a day, and oxybutynin 1⁄2 tb twice a day.

2.2. Dietary Intervention

After following a low-calorie diet with little success in 2009, the subject voluntarily underwent four cycles of a VLCKD for weight loss, which was prescribed by a specialized physician in collaboration with a dietician at the Obesity Center of a northern Italian hospital, as shown in Figure 1. Given the complex medical condition of the subject, each VLCKD cycle lasted 3 months following the European Food Safety Authority (EFSA) guidelines [6] and consisted of three phases. The initial phase of the dietary scheme consisted of three main meals (breakfast, lunch, and dinner) and two snacks, all represented by food replacement products. Then, there was a transition phase where all the food items of the Mediterranean diet were reintroduced both quantitatively and qualitatively, gradually replacing the meal substitutes. The third phase consisted of a balanced diet without meal replacements.

2.3. Data Collection and Analysis

During the diet therapy cycles, the anthropometric and clinical variables of the patient were closely monitored, and the plasmatic parameters regarding renal function, blood glucose, insulin, cholesterol (total, LDL and HDL), uric acid, and urinary values of ketonuria and proteinuria were collected. Bioelectric Impedance Analysis (BIA, InBody230, Biospace Co., Ltd., Seoul, Korea) was used to assess body composition. The InBody analyzer can be used as a surrogate when Dual-Energy X-ray Absorptiometry (DXA) is not available, as demonstrated elsewhere [7]. The data were analyzed retrospectively and are reported in this work. The patient provided written informed consent for the use of his data for further analysis and/or production of scientific reports.

3. Results

The patient underwent several dietary interventions, as shown in Figure 1.

3.1. Hypocaloric Diet

In 2009, the patient’s height was 1.57 m, and his weight was 93.5 kg, with a Body Mass Index (BMI) of 37.93 kg/m², corresponding to grade II obesity; his waist circumference was 110 cm, and his neck circumference was 46 cm. The patient’s eating habits consisted of three main meals a day, at regular times. Lunch was the main meal, usually consumed at home. He reported eating between meals both during the day and in the evening, after dinner. The sense of satiety was preserved, and he preferred bought sweets or chocolate.

The baseline examination, carried out in August 2009, showed insulin resistance, a Homeostatic Model Assessment (HOMA) index of 9.3, mild post-prandial hyperinsulinism, and preserved renal function (creatinine levels were 1.1 mg/dL, with an estimated Glomerular Filtration Rate (eGFR) of between 60 and 89 mL/min/1.73 m²). Initially, the patient underwent a 1500 kcal/day dietary plan with physical activity plus Orlistat 120 mg 1 tb twice a day, along with omega-3 fatty acid supplementation, with an initial benefit on weight loss, followed by weight regain.

3.2. First VLCKD

At the medical check-up in January 2012, body weight was 99.5 kg (+6 kg vs. baseline), BMI 40.36 kg/m² (+2.43 vs. baseline). The impedance analysis showed normal lean mass (49.0 kg) and increased fat mass (51.9 kg). Given the ineffectiveness of previous treatments, the creatinine clearance, and the opinion of the nephrologists, a VLCKD with a protein intake of 0.8 g per kg of ideal weight was suggested. In March 2012, at the patient’s peak weight (103.2 kg, BMI 41.86 kg/m²), a VLCKD (meal replacement-based) was performed, followed by an LCD (low-calorie diet) and an HBD (hypocaloric balanced diet), whose detailed description is available elsewhere [8]. By the end of the first modified ketogenic diet cycle, the subject’s weight dropped to 89.7 kg. Renal function was preserved, as the creatinine values were kept within the normal limits. After this first dietary cycle, the patient followed a hypocaloric diet for a few months. Nevertheless, during this period, he was unable to maintain the weight achieved.

3.3. Second VLCKD

Later, with the intention to lose more weight, a new VLCKD cycle was started, allowing the subject to lose weight until he reached, at the end of the November 2012–January 2013 period, a weight of 81 kg. The laboratory tests, as well as the bioelectrical impedance parameters performed during the cycles of protein ketogenic diet, are reported in

Table 1. Laboratory tests during diet cycles.

	First Cycle		Second Cycle		Third Cycle		Fourth Cycle
	Start	End	Start	End	Start	End	Start	End
Glycaemia, mg/dL	106	94	95	99	93	86	91	84
Insulin, mIU/L	23.9	10.9	15.8	10.3	21.9	16.1	19.2	12.1
HOMA IR	6.26	2.52	3.70	2.51	5.02	3.41	4.31	2.50
Triglycerides, mg/dL	172	100	117	118	169	97	160	150
Total cholesterol, mg/dL	130	135	163	169	179	192	159	194
HDL cholesterol, mg/dL	34	32	41	43	40	40	40	39
LDL cholesterol, mg/dL	110	103	98	104	129	139	124	131
Uric Acid, mg/dL	7.1	6.62	5.8	5.9	5.63	6.46	6.15	5.93
Creatininemia, mg/dL	1.11	1.2	1.05	1.11	1.23	1.33	1.31	1.27
GFR (CKD-EPI), ml/min/1.73 m2	91.2	83.0	91.2	79.0	78.8	71.7	72.5	75.3
Urinary proteins, mg/dL	0	0	0	0	20	20	0	10

Abbreviations: HOMA IR: Homeostatic Model Assessment for Insulin Resistance; HDL: High-Density Lipoprotein; LDL: Low-Density Lipoprotein; GFR (CKD-EPI): Glomerular Filtration Rate, Chronic Kidney Disease Epidemiology Collaboration.

and

Table 2. Bioelectrical impedance parameters during diet cycles.

	First Cycle		Second Cycle		Third Cycle		Fourth Cycle
	Start	End	Start	End	Start	End	Start	End
Body weight, kg	103.2	89.7	92.6	81.0	99.7	89.5	94.9	87.5
BMI, kg/m2	41.9	36.4	37.6	32.9	40.4	36.3	38.5	35.5
BMR, kcal	1448	1426	1466	1440	1470	1504	1446	1504
Fat mass, kg	53.3	40.8	41.8	32.8	48.8	37.0	45.1	35.0
Lean mass, kg	49.9	48.9	50.8	51.6	50.9	52.5	49.8	52.5
Muscular mass, kg	27.7	27.1	28.2	26.8	28.4	29.0	27.7	29.1
Body water, kg	36.7	35.9	37.4	36.8	37.4	38.6	36.7	38.6

. The renal function remained unchanged for the entire duration of the diet therapy cycle.

3.4. Third VLCKD

After a period of about four years, in 2017, the patient returned to the Obesity Center to undertake a new cycle of VLCKD. This loss of follow-up was due to the patient moving out of town. Nevertheless, due to an important work-related stress which importantly affected his emotional eating, the patient recontacted spontaneously the Obesity Center. With this new cycle of the VLCKD, he lost about 10 kg, maintaining renal functionality.

3.5. Fourth VLCKD

In 2018, a fourth cycle of ketogenic diet was undertaken, during which the patient presented some difficulty in establishing the state of ketosis, as well as a sense of poorly controlled hunger, confirmed by the ketur test that the patient self-administered in the morning after waking, two hours after each main meal, and two hours after each snack. The medical staff and the dietician who followed the subject suggested changing the meal substitutes, mainly represented by sweet snacks, with savory snacks. This change to the diet favored the onset of ketosis and a better control of the sense of appetite. At the end of the fourth diet therapy cycle, a weight of 87.5 kg was reached with preservation of muscle mass (29.1 kg) and reduction in fat mass (from 45.1 kg at the beginning of the fourth cycle to 35.0 kg).

During each one of the four dietary cycles, the patient received a supplementation with potassium 660 mg, BID. Overall, the weight loss between the phase prior to the implementation of the ketogenic dietary patterns (103.2 kg in 2012) and the end of the fourth diet therapy cycle (87.5 kg in 2018) was 15.7 kg, as shown in

Table 3. Overall changes in terms of body weight, BMI, fat mass, lean mass, and muscle mass before and after ketogenic diet cycles.

	Before Ketogenic Diet Cycles	After 4 Ketogenic Diet Cycles	% of Variation
Body weight, kg	103.2	87.5	−15.21%
BMI, kg/m2	41.9	35.5	−15.27%
Fat mass, kg	53.3	35	−34.33%
Lean mass, kg	49.9	52.5	+5.21%
Muscular mass, kg	27.7	29.1	+5.05%
Body water, kg	36.7	38.6	+5.17%

and summarized in Figure 2. Regarding the BMI, it presented a decrease (35.5 in 2018 vs. 41.9 kg/m² in 2012). A maintenance of muscle mass was observed (normal range 22.9–27.9 kg), which even showed a slight increase at the end of the diet therapy cycles, going from an initial value of 27.7 kg to 29.1 kg at the end of the treatment. The fat mass, although with fluctuations along with body weight, presented an overall reduction (35.0 kg in 2018 vs. 53.3 kg).

4. Discussion

The prescription of very low-calorie ketogenetic diets to induce a rapid weight loss through a caloric intake lower than 800 kcal (3300 kJ) per day has seen an increase in its clinical use, especially, but not exclusively, in obesity-related conditions [9,10,11,12,13,14]. The VLCKDs remain contraindicated, among other circumstances, in the case of moderate–severe renal failure (Glomerular Filtration Rate, GFR < 60) [9,10,11,12,13,14].

In patients with obesity and chronic kidney disease, weight loss is associated with a reduction in proteinuria and a preservation of eGFR. Consequently, in this type of patient, the adoption of a VLCKD under strict medical supervision can slow down the evolution of the disease and have a protective effect on renal function [15]. This subject, according to the eGFR values measured at the beginning of the diet therapy, presented a second-stage chronic kidney disease [16]. During the cyclic VLCKD, creatinine and eGFR levels remained stable, with no significant renal function deterioration. Therefore, the VLCKD can be considered safe in this patient, as previously demonstrated [16].

Low-carbohydrate diets display greater weight loss, better improvement in systolic and diastolic blood pressure, fasting blood glucose, triglycerides, total cholesterol, and HDL cholesterol, compared to low-fat diets [17].

In particular, a meta-analysis was conducted to study whether VLCKDs (providing <50 g of carbohydrates per day) can reduce weight and cardiovascular risk factors more effectively than conventional LCDs (limited-energy diets, in which less than 30% of energy is provided by fat). The findings show that VLCKDs lead to greater reduction of weight, of triglyceride level and of diastolic blood pressure, while they are associated with increased HDL and LDL cholesterol levels. In addition, the subjects assigned to a VLCKD had a greater weight reduction over the long term than those who followed an LFD [18]; therefore, a VLCKD could be considered a valuable tool for the management of obesity. However, despite the promising results shown by the available literature, it should be noted that few studies present a follow-up period equal to or greater than 12 months. Nowadays, the problem concerning obesity is not only represented by weight loss, but—above all—by maintaining the weight achieved. In fact, most obesity therapies fail in the long term, and this problem is particularly relevant for diet therapies. A study of 53 patients with obesity, in good health (except for their condition of prediabetes), randomly assigned to two groups, VLCKD and LCD, and followed for 12 months, showed that, at the end of the study, the weight loss was of 19.9 ± 12.3 and 7.0 ± 5.6 kg (p < 0.0001) for the VLCKD and LCD groups, respectively, and that over 88% of patients in the VLCKD group had lost more than 10% of the initial weight [19].

The long-term effect of therapeutic diets in obesity treatment represents a challenge at present. A 2016 study showed the effectiveness of a 24-month VLKCD and, in particular, it demonstrated a decrease in visceral adipose tissue and a reduction in the individual disease burden of obesity [20]. Similarly, a modelling study showed how effective interventions that successfully reduce population BMI by 1% or 5% would have a significant impact on obesity-related diseases such as cardiovascular disease, type 2 diabetes, and some cancers [21].

The patient described in the present report was followed for a total of six years (from 2012 to 2018). At the end of this period, although with fluctuations in terms of weight reduction and recovery, an overall significant weight reduction was achieved. The VLCKDs, in addition to being low-carbohydrate diets, provide at least 0.8 g of protein per kg of ideal body weight per day, to preserve the lean mass [22]. The muscle mass of the subject described in this work was 27.7 kg at the beginning of the treatment. During the diet therapy, the lean mass was maintained. This result is interesting and is a proxy of weight loss at the expense of fat mass, which reduced from 53.3 kg in 2012 to 35.0 in 2018.

Physical activity did not play an important role in the management of this patient. He practiced swimming only for 2 h per week. In fact, due an osteomyelitic lesion that occurred in 2003 after a corrective epiphysiodesis surgery for a varus in the right tibia, he had serious difficulties in performing moderate-to-intense physical exercises involving the lower limbs, further complicating the management of his weight.

Through the oxidation of lipids, the sense of satiety and a greater energy expenditure, these types of diets promote weight loss without being associated with negative effects on cardiovascular risk factors [23,24]. The advantages of these types of approaches are also due to the rapid weight loss that leads to a motivating effect on the patient that, combined with the practicality of the meal replacements, leads to a better compliance with the diet [25] and a state of ketosis which helps to suppress the sense of hunger [26,27]. However, achieving ketosis status is not easy for all patients. In this clinical case, particularly during the last cycle of VLCKD, the subject hardly reached ketosis, experiencing a permanent sense of hunger and difficulty to adhere to the diet. This was probably due to the numerous sweet snacks included in the dietary protocol of the first week, which probably delayed the onset of the ketogenic state. Once modified in favor of salty snacks, the subject quickly entered ketosis, as demonstrated by the self-administered ketur tests. Despite the benefits and advantages of the VLCKDs, they are accompanied by some aspects that limit compliance and maintenance, as illustrated briefly in

Table 4. Patient’s personal perspective regarding the VLCKD.

Positive	Negative
Quick and easy weight loss	Reduction of social life
Fairly varied diet with assorted products	Sense of unease and discouragement towards people who eat normally
Dietary products already weighed and easy to consume	Costs
Loss of sense of hunger during the diet
Positive psychological state
Transition phase from the protein diet to the normal diet quite simple to organize

.

5. Conclusions

This case is an example of how, under strict medical supervision, the VLCKD, as well as being effective, as already demonstrated [28,29], proves to be safe even in subjects with a complex clinical picture. During a cyclic ketogenic diet approach, with significant weight loss, lean muscle mass was maintained over time. Moreover, no deterioration of the transplanted kidney function occurred. Therefore, the VLCKD can be considered, since it reduces the BMI and is associated with a reduction in obesity-related diseases (cardiovascular disease, type 2 diabetes, and some cancers) and the individual burden of obesity due to a reduction in disease duration. The VLCKD can be considered a valuable alternative to bariatric surgery, even in a complex and delicate case such as the one presented above.