The spectrum of kidney biopsy findings in patients with morbid obesity.

Morbid obesity, defined as body mass index (BMI) ≥40 kg/m2, affects approximately 8% of United States adults and is a recognized risk factor for chronic kidney disease (CKD). We present the first focused biopsy-based study exploring the range of kidney diseases in this population. Among 3263 native kidney biopsies interpreted at Columbia University in 2017, we identified 248 biopsies from morbidly obese patients. In this cohort with median age of 53.5 years, 56% were female and median BMI was 44.0 kg/m2. Diabetes and hypertension were present in 47% and 81% of patients, respectively. Median estimated glomerular filtration rate (eGFR) was 30 ml/min/1.73 m2, and most patients had nephrotic range proteinuria. Obesity related glomerulopathy (ORG), defined as focal segmental glomerulosclerosis with glomerulomegaly or glomerulomegaly alone, was detected in 73 patients, including 29 with ORG alone and 44 with ORG plus another kidney disease. In contrast, 167 patients had other kidney diseases alone, without ORG, most commonly (in descending order) diabetic nephropathy, acute tubular necrosis, hypertensive nephrosclerosis, IgA nephropathy, membranous nephropathy, and lupus nephritis. In 49% of patients, kidney biopsy yielded a diagnosis predicted to change patient management. The strongest predictor of non-ORG lesions was eGFR <30 ml/min per 1.73 m2, and presentation with nephrotic syndrome or acute kidney injury (with or without background CKD) was more common in non-ORG than ORG. The findings reveal an unexpectedly broad spectrum of kidney pathology beyond metabolic syndrome-associated disorders and highlight the importance of kidney biopsy to guide management and prognosis in the morbidly obese population.

Therapeutic living donor nephrectomy.

Therapeutic living donor nephrectomy is defined as a nephrectomy that is performed as therapy for an underlying medical condition. The patient directly benefits from having their kidney removed, but the kidney is deemed transplantable. The kidney is subsequently used as an allograft for an individual with advanced renal disease. Therapeutic donor nephrectomy can be successfully utilized for a heterogenous cohort of disease processes as both treatment for the donor and to increase the number of suitable organs available for transplantation. We describe four cases of therapeutic donor nephrectomy that were performed at our institution. Of the four cases, two patients elected to undergo therapeutic donor nephrectomy as treatment for loin pain hematuria syndrome; one after blunt abdominal trauma that resulted in complete proximal ureteral avulsion; and the fourth after being diagnosed with a small renal mass. Based on our data presented to the United Network for Organ Sharing Board of Directors (UNOS) in December 2015, living donor evaluation has been made simpler for patients electing to undergo therapeutic donor nephrectomy. UNOS eliminated the requirement for a psychosocial evaluation for these patients. As the organ shortage continues to limit transplantation, therapeutic donor nephrectomy should be considered when appropriate.

Donor APOL1 high-risk genotypes are associated with increased risk and inferior prognosis of de novo collapsing glomerulopathy in renal allografts.

Collapsing focal segmental glomerulosclerosis (cFSGS) in the native kidney is associated with heavy proteinuria and accelerated renal failure. However, cFSGS in the renal allograft is less well characterized. Here we report clinico-pathologic features and APOL1 donor risk genotypes in 38 patients with de novo post-kidney transplant cFSGS. Recipients were 34% female and 26% African American. Concurrent viral infections and acute vaso-occlusion (including thrombotic microangiopathy, cortical necrosis, atheroembolization, and cardiac arrest with contralateral graft thrombosis) were present in 13% and 29% of recipients, respectively. Notably, 61% of patients had concurrent acute rejection and 47% received grafts from African American donors, of which 53% carried APOL1 high-risk genotypes. These frequencies of acute rejection and grafts from African American donors were significantly higher than in our general transplant population (35% and 16%, respectively). Patients had a median serum creatinine of 5.4 mg/dl, urine protein/creatinine 3.5 g/g, and 18% had nephrotic syndrome. Graft failure occurred in 63% of patients at an average of eighteen months post-index biopsy. By univariate analysis, donor APOL1 high-risk genotypes, post-transplant time, nephrotic syndrome, and chronic histologic changes were associated with inferior graft survival while acute vaso-occlusion was associated with superior graft survival. Donor APOL1 high-risk genotypes independently predicted poor outcome. Compared to native kidney cFSGS, post-transplant cFSGS had more acute vaso-occlusion but less proteinuria. Thus, de novo cFSGS is associated with variable proteinuria and poor prognosis with potential predisposing factors of African American donor, acute rejection, viral infection and acute vaso-occlusion. Additionally, donor APOL1 high-risk genotypes are associated with higher incidence and worse graft survival.

Glomerular diseases seen with cancer and chemotherapy: a narrative review.

Glomerular lesions have been recognized in a number of malignant diseases. Membranous nephropathy is the most common glomerular pathology associated with solid tumors. In Hodgkin's disease, the most common lesion is minimal change disease, reflecting possibly an anomaly of T-cell function. On the other hand, in patients with chronic lymphocytic leukemia, a large proportion of glomerular lesions fall into the category of membranoproliferative glomerulonephritis. Membranous nephropathy is also the most common glomerular disease seen following stem cell transplantation, suggesting a possible immune-mediated mechanism. Chemotherapy agents such as interferon, anti-vascular endothelial growth factor agents, tyrosine kinase inhibitors, and bisphosphonates have also been associated with various glomerular diseases and thrombotic microangiopathy. Failure to recognize certain paraneoplastic glomerular diseases can lead to potentially unnecessary therapies. This review describes the association of glomerular diseases with solid tumors, hematological malignancies, stem cell transplantation, and chemotherapeutic agents. We also describe the pitfalls in diagnosis and the dilemma in treating these entities.

Live Donor Renal Anatomic Asymmetry and Posttransplant Renal Function.

BACKGROUND: Relationship between live donor renal anatomic asymmetry and posttransplant recipient function has not been studied extensively. METHODS: We analyzed 96 live kidney donors, who had anatomical asymmetry (>10% renal length and/or volume difference calculated from computerized tomography angiograms) and their matching recipients. Split function differences (SFD) were quantified with technetium-dimercaptosuccinic acid renography. Implantation biopsies at time 0 were semiquantitatively scored. A comprehensive model using donor renal volume adjusted to recipient weight (Vol/Wgt), SFD, and biopsy score was used to predict recipient estimated glomerular filtration rate (eGFR) at 1 year. Primary analysis consisted of a logistic regression model of outcome (odds of developing eGFR>60 mL/min/1.73 m(2) at 1 year), a linear regression model of outcome (predicting recipient eGFR at one-year, using the chronic kidney disease-epidemiology collaboration formula), and a Monte Carlo simulation based on the linear regression model (N=10,000 iterations). RESULTS: In the study cohort, the mean Vol/Wgt and eGFR at 1 year were 2.04 mL/kg and 60.4 mL/min/1.73 m(2), respectively. Volume and split ratios between 2 donor kidneys were strongly correlated (r = 0.79, P < 0.001). The biopsy scores among SFD categories (<5%, 5%-10%, >10%) were not different (P = 0.190). On multivariate models, only Vol/Wgt was significantly associated with higher odds of having eGFR > 60 mL/min/1.73 m (odds ratio, 8.94, 95% CI 2.47-32.25, P = 0.001) and had a strong discriminatory power in predicting the risk of eGFR less than 60 mL/min/1.73 m(2) at 1 year [receiver operating curve (ROC curve), 0.78, 95% CI, 0.68-0.89]. CONCLUSIONS: In the presence of donor renal anatomic asymmetry, Vol/Wgt appears to be a major determinant of recipient renal function at 1 year after transplantation. Renography can be replaced with CT volume calculation in estimating split renal function.