René Verberckmoes

Bartter’s and Gitelman’s Syndromes: From Gene to Clinic

Bartter’s and Gitelman’s syndromes are characterized by hypokalemia, normal to low blood pressure and hypochloremic metabolic alkalosis. Recently, investigators have been able to demonstrate mutations of six genes encoding several renal tubular transporters and ion channels that can be held responsible for Bartter’s and Gitelman’s syndromes. Neonatal Bartter’s syndrome is caused by mutations of NKCC2 or ROMK, classic Bartter’s syndrome by mutations of ClC-Kb, Bartter’s syndrome associated with sensorineural deafness is due to mutations of BSND, Gitelman’s syndrome to mutations of NCCT and Bartter’s syndrome associated with autosomal dominant hypocalcemia is linked to mutations of CASR. We review the pathophysiology of these syndromes in relation to their clinical presentation.

Reversal of hepatorenal syndrome in four patients by peroral misoprostol (prostaglandin E1 analogue) and albumin administration

Four consecutive patients with alcoholic cirrhosis and hepatorenal syndrome were treated with misoprostol, a synthetic methylester prostaglandin E1 analogue at twice the dosage advocated for anti-ulcer therapy (i.e., 0.4 mg four times per day orally) and albumin infusions. The mean urinary output obtained over the 3 days preceding misoprostol administration was 250, 315, 550 and 195 ml per 24 h, respectively, in the four patients, despite adequate volume expansion by plasma albumin to reach normal or high central venous pressure. Diuresis increased to 1450, 2440, 925 and 1300 ml, respectively, on days 2-4 after onset of therapy. Serum creatinine levels were 71, 51, 33 and 35 mg/l before and dropped to 26, 21, 13 and 17 mg/l during treatment. All patients had hyponatraemia (117-128 mequiv/l) which normalized, although they were continued on a low sodium intake of less than 10 mequiv per 24 h. Urinary sodium excretion increased from 0.4-3 mmol per 24 h, to 15-40 in the first two cases and only slightly to 3-5 in the last two patients. Three patients died after 10, 30 and 40 days due to oesophageal bleeding, encephalopathy or pulmonary infection, whereas one patient underwent an orthotopic liver transplantation when her serum creatinine attained a level of 13 mg/l. In the first patient, hepatorenal syndrome recurred 10 days after stopping the misoprostol treatment. High doses of misoprostol in the presence of adequate volume expansion thus seem to produce marked diuresis and creatininuria as well as mild natriuresis.(ABSTRACT TRUNCATED AT 250 WORDS)

Disappearance of Vascular Calcifications During Treatment of Renal Osteodystrophy: Two Patients Treated with High Doses of Vitamin D and Aluminum Hydroxide

In two patients with chronic renal failure, extensive renal osteodystrophy, and vascular calcifications, treatment with high doses of vitamin D3 and aluminum hydroxide was followed by healing of the osteodystrophy and marked resolution of the vascular calcifications. The importance of adequate serum phosphate control during this treatment is stressed. It is postulated that the presence of pathologic bone that was rendered more avid for mineral by the action of vitamin D contributed to the disposal of calcium and phosphorus derived from the calcified vessels and from a positive external balance.

Effect of Hemodialysis On Plasma Kinetics of Fenofibrate in Chronic-renal-failure

The influence of hemodialysis on plasma fenofibric acid kinetics has been investigated in patients with chronic renal failure given 300 mg of fenofibrate in a single oral dose. A very pronounced lengthening of the fenofibric acid plasma decay was observed in both hemodialyzed (n = 6) and nonhemodialyzed (n = 9) patients. Hemodialysis did not modify the plasma levels and the ultrafiltrates contained very small amounts of fenofibric acid. The repeated daily administration of 100 mg of fenofibrate during 2 weeks in 5 renal patients on regular hemodialysis resulted in increasing plasma levels and led to progressive cumulation of fenofibric acid. Plasma fenofibric acid conjugates could not be detected. No particular clinical side effects or increase of CPK, GOT, GPT were be observed.

Primary Sclerosing Cholangitis Associated with Membranous Nephropathy

Excerpt We report the case of a patient with primary sclerosing cholangitis associated with membranous nephropathy. A 41-year-old man had edema and fatigue. Serum albumin was 9.9 g/L (normal, 36 to...

Renal cadaveric transplantation in diabetics using total lymphoid irradiation or cyclosporin A: A controlled randomized study

Abstract. A total of 20 renal transplant patients with end‐stage diabetic nephropathy entered a randomized controlled trial comparing preoperative, fractionated total lymphoid irradiation (TLI) (radiation dose, 20–30 Gy) with postoperative cyclosporin A (CsA). Both groups received postoperative low‐dose methylprednisolone maintenance therapy. The 3‐year patient and graft survival was similar for both groups (100% and 71% in the TLI and 75% and 75% in the CsA group, respectively). Rejection crises occurred significantly more frequently (P < 0.01) in the TLI‐treated recipients. The incidence of infectious or diabetic complications was not significantly different in both groups. It is concluded that TLI and CsA are both effective treatment modalities for cadaveric renal transplantation in diabetics; CsA, however, is superior in preventing rejection crises.

Bicarbonate dialysis using a single concentrate.

Bicarbonate Dialysis Using a Single Concentrate J. Josy Martens D. Didier Hauglustaine R. René Verberckmoes P. Paul Michielsen Josy Martens, MD, Didier Hauglustaine, MD, René Verberckmoes, MD, Paul Michielsen, MD, Division of Nephrology, Universitair Ziekenhuis Gasthuisberg, Herestraat, 49, B-3000 Leuven (Belgium) Dear Sir, Haemodialysis with bicarbonate-containing dialysate may offer many advantages over acetate dialysis as improved vascular stability, prevention of dialysis-induced hypoxaemia, more adequate base repletion and improved patient well-being [1–4]. Bicarbonate dialysis is now more frequently used since automated techniques have been developed to prevent precipitation of calcium and magnesium carbonates. However, the present systems require a two-stream proportioning and monitoring device and two separate concentrates. These systems are more complicated and expensive than those used in standard acetate dialysis [4, 5]. We propose an alternative method for bicarbonate dialysis that circumvents the aforementioned problems. Our method of bicarbonate dialysis uses a single concentrate, composed of sodium chloride and sodium bicarbonate. Calcium, magnesium and potassium chloride are omitted from the dialysate but administered by a continuous intravenous infusion. The concentrate was prepared long in advance by dissolving sodium choride and sodium bicarbonate in deionized water to achieve, after dilution 1/12, a final dialysate composition of Na+ 137 mmol/l, Cl 102 mmol/l and HCOj 35 mmol/l. The concentrate and reverse osmosis water were mixed and monitored by a conventional single patient dialysis machine ( < Monitral > , Hospal). A sterile solution containing CaCl2–2 aqua 51.35 g/l, KC115.53 g/l and MgCl2 · 6 aqua 21.18 g/l, was infused by a calibrated pump at a constant rate of 0.5 ml/min into the blood being returned to the patient (i.e. 7 mg elemental calcium/min [6] and 25 mmol potassium and magnesium/4 h). In the event of a shutdown of the blood pump the infusion was stopped. Table I. Laboratory measurements (preand postdialysis) in 7 patients during six bicarbonate dialysis (mmol/l)

Renal cadaveric transplantation in diabetics using total lymphoid irradiation or cyclosporin A

A total of 20 renal transplant patients with end-stage diabetic nephropathy entered a randomized controlled trial comparing preoperative, fractionated total lymphoid irradiation (TLI) (radiation dose, 20–30 Gy) with postoperative cyclosporin A (CsA). Both groups received postoperative low-dose methylprednisolone maintenance therapy. The 3-year patient and graft survival was similar for both groups (100% and 71% in the TLI and 75% and 75% in the CsA group, respectively). Rejection crises occurred significantly more frequently (P<0.01) in the TLI-treated recipients. The incidence of infectious or diabetic complications was not significantly different in both groups. It is concluded that TLI and CsA are both effective treatment modalities for cadaveric renal transplantation in diabetics; CsA, however, is superior in preventing rejection crises.