Cyclosporine nephrotoxicity and early posttransplant hyperkalemia in living-donor renal recipients: report of 4 cases.

OBJECTIVES: Hyperkalemia is an electrolyte disorder that may occur during the first few months after a renal transplant, in patients undergoing cyclosporine immunosuppression. We present our experience with cyclosporine-associated hyperkalemia in living-donor renal transplant recipients, with isolated clinically relevant hyperkalemia soon after surgery. MATERIALS AND METHODS: We report 4 living-donor renal recipients with hyperkalemia soon after transplant. RESULTS: Severe unexpected hyperkalemia (7.5- 9.4 mmol/L) was noted in our patients 12, 20, 22, and 34 days after transplant. The C2 cyclosporine concentration was within recommended range or slightly greater than 1200 ng/mL. The hypertonic glucose/insulin treatment along with potassium diet was without results. A reduction in daily cyclosporine dosages, along with 1- to 2-week administration of fludrocortisone was effective. The patients became normokalemic taking a standard, triple-drug immunosuppression protocol, and were discharged home with normal renal function. There were no repeat episodes of hyperkalemia in any of the patients during 12 months of follow-up. CONCLUSIONS: Cyclosporine should be considered a cause of hyperkalemia in renal transplant recipients. Successful treatment with fludrocortisone confirms that transitional pseudohypoaldosteronism has a potential nephrotoxic effect of cyclosporine. We recommend close monitoring of the cyclosporine concentration and administering fludrocortisone when treating hyperkalemia in renal transplant recipients.

[Rapidly progressing quadriparesis secondary to licorice (souss) intoxication]. / Tétraparésie rapidement progressive par intoxication à la réglisse (souss).

INTRODUCTION: Regular consumption of licorice based beverages can provoke pseudohyperaldosteronism with hypokalemia but can rarely lead to severe muscle weakness. CASE REPORT: A 62-year-old man was admitted for a one-week history of progressive weakness of the four limbs. Blood work revealed severe hypokalemia that was due to primary pseudo-hyperaldosteronism secondary to licorice intoxication. He became normal after correction of the electrolytes disturbances. DISCUSSION & CONCLUSION: In an area where a liquorice-based beverage (souss), is frequently and sometimes excessively consumed, pseudo-hyperaldosteronism secondary to licorice toxicity should be thought of in front of any muscle weakness accompanied by hypokalemia. A rapid correction of electrolytes disturbances leads to rapid improvement.

Cyclosporine metabolic side effects: association with the WNK4 system.

BACKGROUND: Cyclosporine is used for treatment of transplanted patients and for immune-mediated diseases. Cyclosporine is known to cause a combination of metabolic side effects including hypertension, hyperkalemia, hypercalciuria and hypomagnesemia. These side effects except for hypomagnesemia are the cardinal features of familial hyperkalemia and hypertension (FHHt), also called pseudohypoaldosteronism type II (PHA II). FHHt is caused by mutations in the kinases WNK1 and WNK4 resulting in an increase in renal Na-Cl cotransporter (NCC) apical distribution and function. Therefore, we studied whether cyclosporine's metabolic side effects are mediated by WNK4 and NCC. DESIGN: Sprague-Dawley (SD) rats were treated by cyclosporine 25 mg kg(-1) subcutaneously for 14 days. Blood pressure, blood chemistry values and kidney WNK4 protein were determined. In addition, mDCT cells were exposed to cyclosporine, and their WNK4 mRNA and protein content, and their NCC protein content and phosphorylation were determined. RESULTS: The rats developed an FHHt-like syndrome including hypertension, hyperkalemia and salt-sensitive hypercalciuria. A significant increase in their kidney WNK4 protein content (0·13 ± 0·01 vs. 0·67 ± 0·16 WNK4/GAPDH in controls, P = 0·0183) was found. In mDCT cells, cyclosporine caused a rise in WNK4 mRNA levels and also a threefold rise in WNK4 protein content. This rise was followed by a rise in NCC protein content and pSer71 phosphorylation. CONCLUSIONS: These observations may explain in part the mechanism of cyclosporine-induced hypertension, hyperkalemia and hypercalciuria.

Shakuyaku-kanzo-to induces pseudoaldosteronism characterized by hypokalemia, rhabdomyolysis, metabolic alkalosis with respiratory compensation, and increased urinary cortisol levels.

BACKGROUND: Licorice, the primary ingredient of the Japanese herbal medicine shakuyaku-kanzo-to, can cause pseudoaldosteronism. Thus, shakuyaku-kanzo-to can cause this condition. CASE DESCRIPTION: A 79-year-old woman was brought to the emergency room. She had been experiencing general fatigue, numbness in the hands, and weakness in the lower limbs and could not stand up without assistance. She presented with hypokalemia (potassium level, 1.7 mEq/L), increased urinary excretion of potassium (fractional excretion of K, 21.2%), abnormalities on an electrocardiogram (flat T waves in II, III, AVF, and V1-6), rhabdomyolysis (creatine kinase level, 28,376 U/L), myopathy, metabolic alkalosis with respiratory compensation (O(2) flow rate, 2 L/min; pH, 7.473; pco(2), 61.0 mm Hg; po(2), 78.0 mm Hg; HCO(3), 44.1 mmol/L), hypertension (174/93 mm Hg), hyperglycemia (blood glucose level, 200-300 mg/dL), frequent urination, suppressed plasma renin activity (0.1 ng/mL/hour), decreased aldosterone levels (2.6 ng/dL), and increased urinary cortisol levels (600.6 microg/day; reference range, 26.0-187.0 microg/day). CONCLUSIONS: In this case, the observed reduction in the urinary cortisol levels, from 600.6 to 37.8 microg/day, led to a definitive diagnosis of pseudoaldosteronism instead of the apparent mineralocorticoid excess syndrome. Discontinuing shakuyaku-kanzo-to treatment and administering spironolactone and potassium proved effective in improving the patient's condition. Medical practitioners prescribing shakuyaku-kanzo-to should take into account the association between licorice, which is its main ingredient, and pseudoaldosteronism.

The old lady who liked liquorice: hypertension due to chronic intoxication in a memory-impaired patient.

The authors report an 85-year-old patient admitted because of cognitive impairment. During examination hypertension and hypokalaemia were found. After some time it was discovered that the patient was eating too much liquorice. The case demonstrates that liquorice intoxication should be considered as a cause of hypertension in old age. Furthermore the case demonstrates that missing an intoxication is a pitfall for medical history taking of patients with cognitive impairment.

Cyclosporine a and FK506 inhibit transcriptional activity of the human mineralocorticoid receptor: a cell-based model to investigate partial aldosterone resistance in kidney transplantation.

Renal transplant recipients treated with cyclosporine A (CsA) and FK506 (tacrolimus) develop signs of hypoaldosteronism despite normal plasma aldosterone levels, suggesting a relative resistance of the distal nephron to aldosterone action. To examine the effects of immunosuppressants on human MR (hMR) function, we established the M cell model, renal tubular cells stably transfected with hMR. Upon CsA and FK506 administration, hMR mRNA levels and aldosterone binding in M cells remained unchanged (maximum number of sites, approximately 80 fmol/mg protein; K(d) = approximately 1 nM). Aldosterone-dependent intracellular localization of green fluorescent protein-hMR was not affected by immunosuppressants. A major impact of CsA or FK506 on the multidrug resistance gene product in cellular accumulation of aldosterone was also excluded. In contrast, aldosterone-stimulated hMR transcriptional activity was reduced to 53 +/- 11.2% (P < 0.03) after pretreatment of M cells for 3 d with CsA and to 71 +/- 9.6% (P < 0.05) after pretreatment with FK506. These effects were both time and concentration dependent (IC(50) of CsA, 10(-6) M; IC(50) of FK506, 10(-5) M) and needed at least 2 d to develop. Such an inhibitory effect does not depend on the N-terminal part of hMR, as CsA also reduced transcriptional activity of a 1-453 deletion mutant of hMR. Our results demonstrate that immunosuppressants inhibit hMR transcriptional activity without affecting hMR expression, aldosterone binding properties, and hMR nucleocytoplasmic trafficking. They suggest that ion transport alterations in renal graft recipients are in part induced by impaired hMR function.