Renal Complications Following Lung Transplantation and Heart Transplantation.

Renal complications are common following heart and/or lung transplantation and lead to increased morbidity and mortality. Renal dysfunction is also associated with increased mortality for patients on the transplant wait list. Dialysis dependence is a relative contraindication for heart or lung transplantation at most centers, and such patients are often listed for a simultaneous kidney transplant. Several factors contribute to the impaired renal function in patients undergoing heart and/or lung transplantation, including the interplay between cardiopulmonary and renal hemodynamics, complex perioperative issues, and exposure to nephrotoxic medications, mainly calcineurin inhibitors.

Genome-wide Profiling of Urinary Extracellular Vesicle microRNAs Associated With Diabetic Nephropathy in Type 1 Diabetes.

INTRODUCTION: Diabetic nephropathy (DN) is a form of progressive kidney disease that often leads to end-stage renal disease (ESRD). It is initiated by microvascular complications due to diabetes. Although microalbuminuria (MA) is the earliest clinical indication of DN among patients with type 1 diabetes (T1D), it lacks the sensitivity and specificity to detect the early onset of DN. Recently, microRNAs (miRNAs) have emerged as critical regulators in diabetes as well as various forms of kidney disease, including renal fibrosis, acute kidney injury, and progressive kidney disease. Additionally, circulating extracellular miRNAs, especially miRNAs packaged in extracellular vesicles (EVs), have garnered significant attention as potential noninvasive biomarkers for various diseases and health conditions. METHODS: As part of the University of Pittsburgh Epidemiology of Diabetes Complications (EDC) study, urine was collected from individuals with T1D with various grades of DN or MA (normal, overt, intermittent, and persistent) over a decade at prespecified intervals. We isolated EVs from urine and analyzed the small-RNA using NextGen sequencing. RESULTS: We identified a set of miRNAs that are enriched in urinary EVs compared with EV-depleted samples, and identified a number of miRNAs showing concentration changes associated with DN occurrence, MA status, and other variables, such as hemoglobin A1c levels. CONCLUSION: Many of the miRNAs associated with DN occurrence or MA status directly target pathways associated with renal fibrosis (including transforming growth factor-ß and phosphatase and tensin homolog), which is one of the major contributors to the pathology of DN. These miRNAs are potential biomarkers for DN and MA.

Recurrent Mixed Cryoglobulinemia (MCS): A Case Report and Literature Review.

We report a case of recurrent mixed type II cryoglobulinemia with difficult diagnosis and treatment dilemma and uncertain prognosis in view of limited studies. A 60-year-old male with history of essential mixed cryoglobulinemia 12 years ago treated successfully with six months of cyclophosphamide and prednisone presented with bilateral lower extremity pupuric rash and swelling. He was found to have proteinuria, hematuria, RBC casts, low serum complement levels, and acute kidney injury (AKI). Initial therapy with methylprednisone and oral cyclophosphamide was ineffective (patient developed respiratory failure due to alveolar hemorrhage). Additional labs revealed positive type II cryoglobulins, high free Kappa/Lambda, UPEP with minimal urine protein, SPEP with marked hypogammaglobulinemia, and negative tests for HIV, HCV, ANA, and ANCA. More aggressive therapy with daily plasmapheresis and rituximab was instituted with very good clinical response. He achieved clinical remission but developed another flare 8 months later. Kidney biopsy showed membranoproliferatve glomerulonephritis with cryoglobulin deposits. Flow cytometry and biopsy of bone marrow was consistent with lymphoplasmacytic lymphoma. His diagnosis was eventually confirmed and responded clinically to another course of rituximab and plasmapheresis, but prognosis is yet to be seen.

Impaired renal calcium absorption in mice lacking calcium channel beta 3 subunits.

Transgenic mice lacking calcium channel beta3 subunits (CaVbeta3) were used to determine the involvement of a multimeric calcium channel in mediating stimulated renal calcium absorption. We measured the ability of calcium channel beta3 subunit-null (CaVbeta3-/-) and wild-type (CaVbeta3+/+) mice to increase renal calcium absorption in response to the calcium-sparing diuretic chlorothiazide (CTZ). Control rates of fractional sodium excretion were comparable in CaVbeta3-/- and CaVbeta3+/+ mice and CTZ increased sodium excretion similarly in both groups. CTZ enhanced calcium absorption only in wild-type CaVbeta3+/+ mice. This effect was specific for diuretics acting on distal tubules because both CaVbeta3-/- and CaVbeta3+/+ mice responded comparably to furosemide. The absence of beta3 subunits resulted in compensatory increases of TrpV5 calcium channels, the plasma membrane Ca-ATPase, NCX1 Na/Ca exchanger protein, and calbindin-D9k but not calbindin-D28k. We conclude that TrpV5 mediates basal renal calcium absorption and that a multimeric calcium channel that includes CaVbeta3 mediates stimulated calcium transport.

Drug therapy in transplant recipients: special considerations in the elderly with comorbid conditions.

Elderly patients with end-stage organ failure are now more frequently undergoing transplantation. Medication management in this population is challenging because of the combination of multiple comorbidities, polypharmacy, and immunological, pharmacokinetic and pharmacodynamic changes attributable to the aging process. Immunosuppressive medications can exacerbate pre-existing medical conditions and promote the development of disease processes. Cardiovascular disorders, such as hypertension, coronary artery disease, congestive heart failure and arrhythmias are common in elderly transplant recipients, and account for most of the deaths in this population. Blood pressure, blood glucose and cholesterol control is of particular concern because elderly transplant recipients frequently have or develop these complications. Elderly transplant recipients are commonly receiving anticoagulation therapy with warfarin and are at a higher risk of bleeding, especially if they have renal dysfunction. Infectious complications occur frequently in the transplanted population, with pneumonia being the most common infection seen in hospitalised patients. Attention to vaccination for the prevention of influenza and pneumococcal infections is important because of the increased risk of these diseases in this population. Depression itself has been associated with decreased survival in older individuals, and depression in elderly transplant recipients may be reversible with the administration of pharmacological agents. Effective long-term care of transplant recipients demands an understanding of how particular medications affect clinical evaluation and treatment. This article addresses some of the practical issues surrounding medication management and prevention of these particular problems in elderly transplant recipients.