Diet in Renal Diseases: An Art of Science

Purpose of Review: Chronic kidney disease (CKD) is associated with a limited ability to excrete fluids, electrolytes, uremic toxins and other end-products of catabolism. Studies on adverse renal outcomes with dietary patterns are limited. Methods: Comprehensive search in PubMed of papers published until June 2024 describing prospective cohort studies on renal nutritional therapy (RNT) with at least 3 years of follow up. Results: RNT should include adequate yet limited amounts of calories, fluids, protein, lipids, sodium, potassium, and phosphorus. RNT is an adjuvant to specific drug-therapy in 1) certain complications viz. fluid overload, anemia and renal osteodystrophy, and 2) specific kidney diseases viz. glomerulopathies, tubulopathies, polycystic kidney disease, calcium oxalates urolithiasis and cystinuria, as well as 3) types of renal failure viz acute and chronic and its treatment viz. hemodialysis, peritoneal and transplantation. Conclusion: RNT is patient-specific and should be systematically planned to delay the progression of CKD as well as to prevent and treat its complications.

The Beneficial Effect of 12-Hour Fasting, 45 Minutes Exercise Thrice Weekly and Their Combination on Weight Loss, Anthropometric Measures and Metabolic Syndrome

Background: Obesity is the leading preventable cause of death worldwide. It is associated with significant increases in morbidity and mortality. Few studies have addressed, prospectively, the impact of life-style modification in weight-reduction in 1) morbidly obese patients with BMI > 35 kg/m2 and 2) on its associated co-morbid risk factors for metabolic syndrome viz. high blood pressure, diabetes, hyperlipidemia and steatohepatitis as well as psychiatric disorders. Patients and Methods: We prospectively evaluated the role of 1) two meals daily with in between 12-hour fasting, 2) thrice weekly 45-minute active-walk, and 3) their combination, in management of ambulant obese patients, at BMI of 35 to 39.9 kg/m2 who had such multiple acquired metabolic disorders. The study was conducted over 3 years with 45 patients in 3 matched groups with regards to gender, age, BMI, waist circumference, lipid profile (LDL and TG), fibroscan steatosis grade, psychiatric assessment, antidiabetic drugs and antihypertensive ones. Results: At 6 and 12 months, the 3 regimens were well tolerated and were effective in weight loss, improvement in anthropometric measures and management of metabolic syndrome yet the combined one was significantly better in all endpoints. Conclusion: Our protocols of exercise and dieting were effective measures in managing obesity and its associated co-morbidities and their combination is synergetic.

The Deleterious Effect of Inappropriate Calcium and Vitamin D Supplementation during Pregnancy in Women Predisposed to Calcium Oxalate Urolithiasis

Background: Gestational formation of new urolithiasis is rare yet the impact of inappropriate gestational calcium and vitamin D supplementation (Ca/DS) is underestimated. Patients and Methods: we retrospectively evaluated 75 pregnant women with history of UL, yet were stable for >2 years on dietary restrictions, for new UL after Ca/DS. Results: During the past 5 years 21 (48%) of those who had received Ca/DS had developed UL and all had high Vitamin D with hypercalcemia while the remaining 31 patients, without Ca/DS, did not have UL and maintained normal vitamin D urinary calcium without need for supplementation. Overt UL was evident by 30th weeks of gestations and most were diagnosed by ultrasonography and managed by medical expulsive therapy. Conclusion: in patients with history of UL, prudent use of Ca/DS is indicated to avoid new UL.

Propensity for Progressive Renal Disease in Nephroangiosclerosis: A Refractory Phenotype of Genetic Vasculopathy in Essential Hypertension

Background: Inadequate treatment of essential hypertension (EH), Obesity, smoking, carbohydrate intolerance, hyperlipidemia, and nephrotox-in-exposure are major confounding factors in progression of Nephroangiosclerosis (N). However, neither the prevalence nor the severity of EH is a reliable predictor of individuals at risk for subsequent nephropathy. Patients and Methods: A 10-years retrospective analysis of 165 adequately treated patients with EH. Results: We observed 2 different renal outcomes. Twenty-three (14%) patients manifested progressive renal disease with > doubling serum creatinine and proteinuria with 3 reaching end-stage kidney disease. At start, biopsy of those patients showed features of “benign” nephroangiosclerosis (N) ± secondary form of focal and segmental glomerulosclerosis (without immune deposits). On the other hand;142 with similar demographic characteristics, duration and severity of disease did not show significant renal disease on follow up. Conclusion: Induction of progressive N, in patients with EH, is compatible with phenotypic susceptibilities of genetic disorders.

The Beneficial Effect of Renin-Angiotensin-Aldosterone System Blockade in Treatment of Hypertension, Resistant to Conventional Antihypertensives, in Patients on Maintenance Hemodialysis

Background: Hypertension (HTN) is present in up to 90% of end stage kidney disease (ESRD) patients irrespective of the etiology of their kidney disease. Moreover, it is an important modifiable risk factor for progression to ESRD and its overall cardiovascular morbidity and mortality. Objective: to evaluate, prospectively, the role of Renin-Angiotensin-Aldosterone System blockade (RAAS) in HTN, resistant to 3 conventional antihypertensives, in patients on maintenance hemodialysis (MHD). Patients and methods: A total of 52 such patients were treated with Ramipril and 5 with Losartan after intolerable cough/shortness of breath following Ramipril-use. None of the patients had fluid depletion, renal artery stenosis and primary endocrinopathy. The study group was compared to a matched control group of MHD patients with normal blood pressure following 3 drugs-combination therapies. Results: All patients, with resistant HTN, had significant activation of RAAS system prior to treatment compared to inactive one in the control group. In those with resistant HTN, control of HTN, was established within 2 weeks of therapy and was associated with suppression of the RAAS. Such therapy was associated with minor side effects. Conclusion: Our study has shown that RAAS blockade is safe and effective in controlling such resistant HTN in MHD patients.

Reversible Chronic Interstitial Nephritis Induced by Tacrolimus —Tacrolimus Chronic Interstitial Nephritis

Calcineurin inhibitors (CNI) are potent immunosuppressive agents in prophylaxis against graft rejection and autoimmune diseases including primary glomerulopathies. Previous research showed reversible;acute afferent arteriolar vasculopathy and irreversible chronic interstitial fibrosis associated with CNI nephrotoxicity. In this case report we describe a patient, with minimal change disease, that had developed chronic and progressive renal disease while receiving therapeutic dose of Tacrolimus. His serum creatinine had reached 537 umol/L and his nephrotic state worsened. Kidney biopsy showed chronic interstitial nephritis. Tacrolimus was discontinued and he was treated with 1 mg/kg prednisone in addition to Mycophenolate mofetil (MMF) 1 g twice daily. By the 2nd month;serum creatinine returned to normal and by the 3rd month serum albumin too. After 1 month of therapy;the dose of Prednisone was tapered down gradually till 5 mg daily by the end of 3rd month. Moreover, the dose of MMF was reduced to 500 mg X2 by the end of 3rd month. After 2 years of follow up;he remained stable and without relapse of NS or renal failure. In conclusion, reversible renal disease, due to chronic interstitial nephritis can be induced by CNI which is amenable to treatment with Prednisone and MMF.

Transient D-Penicillamine-Induced Nephrogenic Diabetes Insipidus during Treatment of a Patient with Cystinuria —D-Penicillamine-Induced Nephrogenic Diabetes Insipidus

Background: Diabetes insipidus (DI) is a rare disorder characterized by inappropriate polyuria and hypo-osmolar urine. It is caused by inadequate production of antidiuretic hormone, in response to hypothalamic osmoreceptor-stimulation, from the pituitary gland (central DI) or resistance to its action at terminal distal convoluted tubules and collecting ducts (nephrogenic DI). Most cases of nephrogenic DI are caused by drugs, especially chronic lithium use. The Case: A 46-year-old man manifested such a disorder 8 months following d-Penicillamine (d-P) therapy for cystinuria. The drug was discontinued and the patient was managed conservatively with high fluid intake, diet low in protein and salt as well as alkalization of urine with Urolyte U to a pH > 7.5. Six weeks later, such side effect disappeared. Our patient had developed such phenomenon: a) without significant liver or renal disease to account for cumulative toxicity, and b) with a conventional dosage range of d-P. Such isolated toxicity indicates inherited a predisposition to this side effect. Conclusion: DI is a potential side effect of d-P therapy that is nephrogenic in site, transient in prognosis and an isolated phenomenon likely to reflect genetic predisposition.

The Beneficial Effect of Combination of Mycophenolate with Low-Dose Corticosteroids and Calcineurin-Inhibitor as Well as Angiotensin-Converting Enzyme Inhibitor or Angiotensin II Blocker in Induction and Maintenance of Remission in Corticosteroid- and Rituximab-Resistant Minimal Change Nephrotic Syndrome in Adults

Management of steroid-resistant minimal change disease remains elusive with international guidelines suggesting high-dose corticosteroids and/or Calcineurin inhibitors for months similar to those with refractory idiopathic FSGS. Unfortunately, with such approach, the overall remission rates were 47% - 66%. Moreover, complete remission rates were 32% - 47% and partial remission ones were 19% - 29%. Those limited options of treatment and their poor outcomes led us to conduct the present study to assess the efficacy and safety of a new combined drug-therapy at induction and subsequent maintenance of such disease. The regimen consisted of an initial induction phase of 3-month Prednisone, Calcineurin-inhibitor, Mycophenolate and ACEI/ARB. The latter was followed by a maintenance phase of minimal dose Prednisone and nearly 1/2 the induction dose of Calcineurin inhibitors to decrease their long-term side effects. The results were satisfactory with 14 of the 22 patients, had complete remission. Moreover, 5 patients manifested partial remission and only 3 did not respond. Creatinine clearance was maintained in patients with complete remission yet, was mildly reduced in the partial and non-responsive ones. The safety and efficacy of such new combined drug-therapy provide new tool and future prospective in management of such relentless disease.

Three-Month-Induction Therapy with Prednisone and Mycophenolate Followed by Maintenance Therapy with Mycophenolate Alone for 2 Years: An Effective and Safe Autoimmune Treatment for Triggering Factors Adults with Acute Non-Crescentic Nephritis Associated with Henoch-Schönlein Purpura

Background: Henoch-Schönlein purpura (HSP) is an acute systemic disorder characterized by IgA associated vasculitis. The available data indicate an inherited predisposition to disease with triggering autoimmune phenomena. Hence, we evaluated prospectively the role of a new autoimmune regimen in treatment of its severe nephrotic/nephritic flares associated with non-crescentic nephritis in adult patients. Patients and methods: The regimen consisted of an initial induction phase of 3-month Prednisone and Mycophenolate followed by a maintenance phase of Mycophenolate alone for 2 years. Results: They were satisfactory with complete remission in 5 of 7 patients and partial in 2. Creatinine clearance was normalized in patients with complete remission and remained stable in the partially-responsive ones. Conclusion: Our study has shown the short- and long-term safety and efficacy of such autoimmune regimen directed towards the autoimmune triggering factors in severe forms of non-crescentic HSP.

Sequential Combination Diuretic-Therapy for Massive Fluid Overload in Furosemide-Refractory Patients with Diabetic Kidney Disease

Patients with renal disease are at risk of fluid overload which escalates as the disease progresses. In the present study, we evaluated the efficacy of sequential combination diuretic-therapy (SCDT) in management of massive fluid overload in Furosemide-refractory renal patients. The added diuretics were Spironolactone 25 mg daily for 3 days, to those without risk of hyperkalemia, followed by Hydrochlorothiazide 25 mg/Metolazone 5 mg daily for 3 more days. Excluded patients were those with 1) acute renal disease, 2) echocardiographic evidence of: a) left ventricular ejection fraction < 40%, b) significant stenotic or incompetent valvular disease, c) ASD or VSD, d) significant pericardial disease, and 3) significant limb venous disease or on drugs likely to cause limb-oedema. To assess the extent of fluid overload;clinical examination was complemented with radiological imaging as well as echocardiographic measurement of systolic pulmonary arterial pressure (sPAP). SCDT led to significant symptomatic, clinical, and radiological improvement of fluid overload without significant side effects. The latter were limited to hyperkalemia and hyponatremia which improved with dietary compliance. Moreover, hyperkalemia improved after subsequent addition of Thiazide/Metolazone. SCDT led to significant (p < 0.001) increase in fractional excretion of sodium and decrease in body weight and sPAP. In conclusion;SCDT is a safe and efficacious measure to control fluid overload in patients with renal diseases.

A Problem-Solving in a Case of Medullary Nephrocalcinosis

Medullary Nephrocalcinosis (MNC) is defined as calcium deposition in tubular basement membrane and interstitium of the kidney medulla. It is 20 times more common than cortical one. In this case report, we present a 12-year-boy who presented with persistent nocturnal enuresis for 8 years. Physical examination and routine tests were normal except for microscopic hematuria. Renal ultrasound showed extensive MNC. Twenty-four-hour urine collection revealed normal mineral metabolic screen with low urinary excretion of calcium, phosphorous, magnesium and uric acid yet high for oxalates. Hence, and based on the above-mentioned data, certain metabolic disorders were ruled out: 1) hyperparathyroidism, 2) excessive intake of vitamin D, 3) hypercalcemia, 4) hypercalciuria, 5) hyperuricemia, 6) hyperuricosuria, 7) hypocitraturia, 8) cystinuria, 9) lysinuria and 10) distal renal tubular acidosis were ruled out. Subsequently, urine testing showed high concentration of glycolate with low glycerate and 4-hydroxy-2-oxoglutarates establishing diagnosis of type 1 primary hyperoxaluria (PH I). Further confirmatory tests included: 1) kidney biopsy which showed typical crystals deposition, 2) liver biopsy that confirmed deficiency of the liver-specific peroxisomal enzyme alanine: glyoxylate aminotransferase (AGXT), and 3) full gene analysis that confirmed gene mutation. In conclusion, our case report provides practical algorithm for establishing diagnosis in MNC which is not renal-limited and its prognosis depends upon the underlying etiology.