mycophenolic-acid and Hyperkalemia

Pancreas-kidney transplant is an effective treatment for patients with insulin-dependent dabetes and chronic renal failure. Reduction in technical failure loss and early acute rejection rates contributed to prolong pancreas graft survival. However, drug toxicity affects negatively both short- and long-term follow-ups.. This article reviews the existing literature and knowledge of the immunosuppressive drugs that are frequently used in pancreas transplant, including calcineurin inhibitors, sirolimus, corticosteroids, and mycophenolate. The article also discusses the short- and long-term adverse effects of these drugs. The article also reports and discusses the most relevant in vitro studies, providing additional information to in vivo findings. Some clinically relevant drug interactions with immunosuppressive drugs are also highlighted. Over- and underimmunosuppression effects will not be addressed.. Immunosuppressive regimen after pancreas transplant is very effective and contributed to pancreas allograft survival. However, they present several side effects that are potentiated when drugs are combined. Modifiable and non-modifiable risk factors can aggravate metabolic and toxicological effects of immunosuppressive drugs. It is important to critically analyze the results of clinical studies and investigate new immunosuppressive drugs and/or novel drug combinations. It is equally important to comprehend and interpret experimental data. Therefore, minimization of side effects, based on safe approaches, can prolong pancreas allograft survival.

Topics: Adrenal Cortex Hormones; Bone Diseases; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Gastrointestinal Diseases; Graft Rejection; Graft Survival; Hematologic Diseases; Humans; Hyperkalemia; Hyperuricemia; Immunosuppressive Agents; Mycophenolic Acid; Nervous System Diseases; Pancreas Transplantation; Pneumonia; Renal Insufficiency, Chronic; Sirolimus

As corticosteroid-sparing protocols are increasingly utilized in kidney transplant recipients, it is crucial to understand potential drug interactions between tacrolimus (TAC) and the effect of corticosteroid withdrawal as well as to characterize dose adjustments of mycophenolate mofetil (MMF) in this setting. This prospective, multicenter, randomized, double-blind study included 397 patients who were randomized on posttransplant day 8 to receive either placebo (CSWD) or corticosteroid continuance (CCS). TAC trough levels at week two posttransplant were significantly greater in the CSWD group whereas TAC doses were comparable to the CCS group. This interaction was not observed in the African American subgroup. Higher serum creatinine and potassium levels were also observed in the CSWD group. MMF dose was significantly reduced in the CSWD group by the investigators because of decreased WBC counts, mostly outside of study protocol criteria, despite similar incidence of neutropenia and reported cytomegalovirus infection. Understanding TAC and MMF exposure in the context of corticosteroid-sparing protocols should allow for improved dosing of immunosuppressants and better management of posttransplant patients.

Topics: Adrenal Cortex Hormones; Adult; Black or African American; Body Mass Index; Double-Blind Method; Female; Humans; Hyperkalemia; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Renal Insufficiency; Tacrolimus

Full house nephropathy is defined as the simultaneous detection of IgA, IgG, IgM, C3, and C1q deposits by immunofluorescence, usually indicating lupus nephritis. There are patients with this immunofluorescence pattern, but with negative autoantibody serology, which means they cannot be diagnosed with systemic lupus erythematosus. Patients presenting with full house nephropathy but no other criteria for lupus are diagnosed as having nonlupus full house nephropathy.\ Here, we describe two cases: A male patient who debuted with rapidly progressive glomerulonephritis and a female patient with nephrotic syndrome. Both had negative autoantibody serology, findings in the renal biopsy of class IV lupus nephritis and afull house immunofluorescence pattern. Histological findings in non-lupus full house nephropathy are similar to those in lupus nephritis and, probably, similar physiopathological bases. However, prospective studies are needed to determine risk factors and the renal prognosis and to make suggestions for specific treatments.. La nefropatía full house se refiere a la detección simultánea de depósitos de IgA, IgG, IgM, C3 y C1q en la inmunofluorescencia, lo que generalmente indica la presencia de nefritis lúpica. Hay pacientes con este patrón de inmunofluorescencia, pero con serología negativa para autoanticuerpos, por lo que no se les puede diagnosticar un lupus eritematoso sistémico. Este tipo de nefropatía, en la que no se presentan otros criterios para lupus, se denomina nefropatía full house no lúpica. En esta presentación, se describen dos casos: un paciente que ingresó con una glomerulonefritis rápidamente progresiva y una paciente con síndrome nefrótico, ambos con serología negativa para autoanticuerpos, hallazgos en la biopsia renal indicativos de nefritis lúpica de clase IV y un patrón full house en la inmunofluorescencia. La nefropatía full house no lúpica tiene rasgos histológicos similares a los de la nefritis lúpica y, probablemente, sus bases fisiopatológicas son parecidas. Sin embargo, se necesitan estudios prospectivos para conocer los factores de riesgo y el pronóstico renal, y poder hacer sugerencias sobre tratamientos específicos.

Topics: Adolescent; Antihypertensive Agents; Child; Complement C1q; Complement C3; Diagnosis, Differential; Female; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Hyperkalemia; Immunoglobulins; Immunosuppressive Agents; Kidney Glomerulus; Lupus Nephritis; Male; Mycophenolic Acid; Nephrotic Syndrome; Pregnenediones; Renal Dialysis

Nephrotoxicity is one of the most common side effects of long-term immunosuppressive therapy with calcineurin inhibitors. We describe a case of distal renal tubular acidosis secondary to tacrolimus administration. A 43-year-old man with end-stage liver disease due to hepatitis C and B virus infections and alcoholic cirrhosis received a liver transplantation under immunosuppressive treatment with tacrolimus and mycophenolate mofetil. In the postoperative period, the patient developed hyperkalemic hyperchloremic metabolic acidosis, with a normal serum anion gap and a positive urinary anion gap, suggesting distal renal tubular acidosis. We excluded other causes of hyperkalemia. Administration of intravenous bicarbonate, loop diuretics, and oral resin exchanger corrected the acidosis and potassium levels. Distal renal tubular acidosis is one of several types of nephrotoxicity induced by tacrolimus treatment, resulting from inhibition of potassium secretion in the collecting duct. Treatment to correct the acidosis and hyperkalemia should be promptly initiated, and the tacrolimus dose adjusted when possible.

Topics: Acidosis, Renal Tubular; Administration, Oral; Adult; Bicarbonates; Cation Exchange Resins; Drug Therapy, Combination; Humans; Hyperkalemia; Immunosuppressive Agents; Liver Cirrhosis, Alcoholic; Liver Transplantation; Male; Mycophenolic Acid; Polystyrenes; Sodium Potassium Chloride Symporter Inhibitors; Tacrolimus; Treatment Outcome