A multi-center retrospective cohort study defines the spectrum of kidney pathology in Coronavirus 2019 Disease (COVID-19).

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney.

Early inhibition of the renin-angiotensin system improves the long-term graft survival of single pediatric donor kidneys transplanted in adult recipients.

Transplanting single pediatric donor kidneys into adult recipients has an increased risk of hyperfiltration injury and graft loss. It is unknown if renin-angiotensin system (RAS) blockers are beneficial in this setting. We retrospectively analyzed 94 adults who received single kidneys from donors <10 years old during 1996-2009. The recipients were divided into group 1 with RAS blockers (n = 40) and group 2 without RAS blockers (n = 54) in the first year of transplant. There was no significant difference in any donor/recipient demographic between the two groups. Graft function, incidence of delayed graft function, acute rejection, and persistent proteinuria were not statistically different either. Kaplan-Meier estimated death-censored graft survivals were significantly better in group 1 than in group 2: 95 vs. 81.2%, 82.4 vs. 61.2%, 72.6 vs. 58.5%, and 68.5 vs. 47.2% at 1, 3, 5, and 7 years, respectively (log rank P = 0.043). Multivariable analysis found persistent proteinuria was a risk factor for graft loss (OR 2.70, 95% CI 1.33-5.49, P = 0.006), while RAS blockers reduced the risk of graft loss (OR 0.38, 95% CI 0.18-0.79, P = 0.009). Early RAS blockade therapy in the first year of transplant is associated with superior long-term graft survival among adults transplanted with single pediatric donor kidneys.

Long-term outcome of highly sensitized African American patients transplanted with deceased donor kidneys.

Undertaking transplantation in highly sensitized African American (AA) patients as transplant recipients represents a unique challenge. We retrospectively compared the outcomes of AA with non-African American (NAA) patients who had panel reactive antibody >80% and received deceased donor (DD) kidneys by virtual crossmatch. Immunosuppressive regimen included basiliximab induction and tacrolimus, mycophenolate acid and steroids maintenance. Among 835 consecutive transplants from 1998 to 2007, 142 (17%) were sensitized patients including 89 (16.6%) AA and 53 (17.7%) NAA patients. The AA group had similar 5-year incidence of acute rejection as NAA group (21.4% vs. 26.4%, P = 0.25). Kaplan-Meier estimated graft survival at 1, 3 and 5 years were 91%, 85% and 82% in AA group, and 94%, 79% and 71% in NAA group (P = 0.08). The death-censored graft survival at 1, 3, and 5 years were 93%, 86% and 84% in AA group, and 96%, 83% and 78% in NAA group (P = 0.11). The 1, 3, and 5 years patient survivals were 93%, 88% and 85% in AA group, and 96%, 96% and 94% in NAA group (P = 0.17). Highly sensitized AA patients could be transplanted with DD kidneys at a similar rate as NAA patients, and they may not have a higher incidence of rejection or an inferior graft survival than NAA patients.

The effects of body mass index on graft survival in adult recipients transplanted with single pediatric kidneys.

BACKGROUND: There is insufficient data on the impact of recipient body mass index (BMI) on the long-term graft survival of adult patients transplanted with single pediatric kidneys. METHODS: We performed a retrospective analysis of adult patients transplanted with single pediatric kidneys at our center. The recipients were classified into 2 groups: group 1 (BMI > or =30) and group 2 (BMI <30). Donor/recipient demographics, postoperative outcomes and survival rates were compared between the 2 groups. RESULTS: There was no significant difference in donor/recipient demographics between the 2 groups. In group 1, the death-censored graft survival (DCGS) at 1, 3 and 5 years was 90% at all 3 time points, and in group 2 it was 86, 68 and 60%, respectively (p = 0.05). The mean glomerular filtration rate (with standard deviation in parentheses) at 1, 3 and 5 years was, respectively, 55 (15), 59 (19) and 55 (28) ml/min for group 1, compared to 65 (28), 69 (23) and 67 (20) ml/min in group 2 (p = NS). Multivariate analysis revealed a hazard ratio of 5.12 (95% confidence interval 1.06-24.7; p = 0.04) for graft loss in nonobese patients when compared to obese patients. Obese patients had an increased risk for acute rejections within the first month of transplant (p = 0.02). CONCLUSION: Patients with a BMI > or =30 transplanted with single pediatric kidneys have better DCGS rates when compared to nonobese patients.

Management of metabolic bone disease in kidney transplant recipients.

Bone disease after kidney transplantation has a complex pathophysiology and heterogeneous histology. Pre-existing renal osteodystrophy may not resolve completely, but continue or evolve into a different osteodystrophy. Rapid bone loss immediately after transplant can persist, at a lower rate, for years to come. These greatly increase the risk of bone fracture and vertebral collapse. Hypovitaminosis D, hyperparathyroidism and hyperaluminemia may resolve after kidney transplant, but many patients have other risk factors of bone loss, such as steroids usage, hypogonadism, persistent hyperparathyroidism, poor allograft function, aging, and chronic diseases. Clinical management requires a comprehensive approach to address the underlying and ongoing disease processes. Successful prevention of bone loss has been shown with vitamin D analogues, bisphosphonates and calcitonin. Novel approaches to restore the normal bone remodeling and improve the bone quality may be needed in order to effectively decrease bone fractures in kidney transplant recipients.

Living donor kidney transplantation: medical, legal, and ethical considerations.

The use of living donor kidneys has dramatically increased the number and success of kidney transplants across the world. But questions remain regarding the subjection of a healthy individual to surgery for the benefit of another. Donors do have medical and financial risks. The stigma of organ brokering remains today, with evidence of commercial transplantation in other countries. Here in the US, we are exposed to advertising for donors using the media. In the hope of increasing living donations, we run the risk of stretching altruism too far. In this manuscript, we highlight and discuss some of the current controversies surrounding living donor kidney transplantation across the world.

Pancreas transplantation--a controversy in evolution.

Pancreas transplantation has been mired in controversy throughout its existence. Arguments have erupted regarding its actual indications, the way the surgical procedure should be performed, its benefits, and today, the concept of pancreas islet cell transplantation remains controversial as well. If diabetic patients had a choice between life long insulin therapy and a major operation with immunosuppression afterward, what would they choose? The answer may not be as easy as one thinks. Pancreas transplantation has come a long way. This manuscript discusses the history of pancreas transplantation, how the indications are starting to be defined, evolution of the surgical procedure, current success rates of this procedure, the current scenario of pancreas islet transplantation, and newer developing technologies.

Long-term outcome of ketoconazole and tacrolimus co-administration in kidney transplant patients.

AIM: To study the long-term outcome of ketoconazole and tacrolimus combination in kidney transplant recipients. METHODS: From 2006 to 2010, ketoconazole was given in 199 patients and was continued for at least 1 year or until graft failure (Group 1), while 149 patients did not receive any ketoconazole (Group 2). A combination of tacrolimus, mycophenolate and steroid was used as maintenance therapy. High risk patients received basiliximab induction. RESULTS: Basic demographic data was similar between the 2 groups. The 5-year cumulative incidence of biopsy-confirmed and clinically-treated acute rejection was significantly higher in Group 1 than in Group 2 (34% vs 18%, P = 0.01). The 5-year Kaplan-Meier estimated graft survival (74.3% vs 76.4%, P = 0.58) and patient survival (87.8% vs 87.5%, P = 0.93) were not different between the 2 groups. Multivariable analyses identified ketoconazole usage as an independent risk of acute rejection (HR = 2.33, 95%CI: 1.33-4.07; P = 0.003) while tacrolimus dose in the 2(nd) month was protective (HR = 0.89, 95%CI: 0.75-0.96; P = 0.041). CONCLUSION: Co-administration of ketoconazole and tacrolimus is associated with significantly higher incidence of acute rejection in kidney transplant recipients.