Therapeutic apheresis in kidney transplantation: Emerging trends.

INTRODUCTION: The use of therapeutic apheresis (TA) either as stand-alone or adjunctive treatment in kidney transplantation has increased over the years to become a leading indication. This study shows recent trends in indications for TA related to kidney transplantation, adverse events, and patient outcome in this cohort. METHODS: This is a retrospective cohort review of adults who received TA for kidney transplant-related indications from January 1, 2017, to December 31, 2022, at the University of Virginia Medical Centre, Charlottesville, VA, USA. Data extracted include basic demographics, indication for apheresis, number of procedures, procedure characteristics, procedure-related adverse events (complications), and serum ionized calcium and serum creatinine. Data were analyzed using statistical package for social sciences (SPSS 2022 IBM Inc). RESULTS: Data from a total of 131 patients who received 860 TA procedures were analyzed. Indications for TA were antibody-mediated rejection (65.5%), recurrent focal segmental glomerulosclerosis (15%), thrombotic microangiopathy (5%), desensitization for ABO incompatibility (4.5%) and for HLA-incompatibility (4.5%), and recurrent IgA nephropathy (1%). Some adverse events were encountered in 16.7% of the procedures and include hypocalcemia (7%), vascular access malfunction (0.7%), hypotension (1.2%), arrhythmia (0.6%), and depletion coagulopathy (0.6%). The overall case mortality rate was 8.4% over the 6-year period. There was one death recorded on machine during TA resulting in a procedure-mortality rate of 0.12%. CONCLUSION: Antibody-mediated rejection was the most common indication for TA related to kidney transplantation. Adverse events were minor and patient survival over the time was within usual limits.

Clinical Predictors and Prognosis of Recurrent IgA Nephropathy in the Kidney Allograft.

Introduction: Although IgA nephropathy (IgAN) is the most common recurrent glomerulonephritis encountered in the kidney allograft, the clinical and immunogenetic characteristics remain poorly understood. We sought to study determinants and prognosis of recurrent IgAN with special focus on HLA antigens. Materials and Methods: Between 2005 and 2019, we identified 282 transplanted patients with failure secondary to IgAN from two North American and one European Medical Centers, including 80 with recurrent IgAN and 202 without recurrence. Prevalence of HLA antigens was compared to external healthy controls of European ancestry (n=15,740). Graft survival was assessed by Kaplan-Meier method and log rank test. Cox proportional hazards were used for multivariable analyses. Results: Compared to external controls of European ancestry, kidney transplant recipients of European ancestry with kidney failure secondary to IgAN had higher frequency of HLA-DQ5 (42% vs. 30%, OR=1.68, P=0.002) and lower frequency of HLA-DR15 (15% vs. 28%, OR=0.46, P<0.001) and HLA-DQ6 (32% vs. 45%, OR=0.59, P=0.003); however, the frequency of these HLA antigens were similar in recurrent versus non-recurring IgAN. Younger recipient age at transplantation was an independent predictor of recurrence. HLA-matching was an independent predictor for recurrent IgAN only in recipients of living-related but not deceased or living unrelated transplants. Recurrent IgAN was an independent predictor of allograft failure, along with acute rejection. In patients with recurrent IgAN, serum creatinine at biopsy, degree of proteinuria, and concurrent acute rejection were associated with inferior allograft survival. Discussion/ Conclusion: Recurrent IgAN negatively affects allograft survival. Younger recipient age at transplantation is an independent predictor of recurrent IgAN, while the presence of HLA antigens associated with IgAN in the native kidney and HLA-matching in recipients of deceased or living unrelated transplants are not.

Immunosuppression and Kidney Transplantation.

Immunosuppression is complex, fraught with on-target and off-target adverse effects, and hard to get right but is the key to successful allotransplantation. Herein, we review the key immunosuppressive agent classes used for kidney transplant, highlighting mechanisms of action and typical clinical use.

Clinicopathologic Assessment of Monoclonal Immunoglobulin-associated Renal Disease in the Kidney Allograft: A Retrospective Study and Review of the Literature.

BACKGROUND: Monoclonal immunoglobulin (MIg)-associated renal disease (MIgARD) comprises a group of disorders caused by direct deposition of paraproteins in the kidney. Allograft MIgARD is infrequently encountered and poorly characterized. METHODS: First, we assessed our allograft biopsies diagnosed with MIgARD between 2007 and 2018. The cohort included the following 26 patients: proliferative glomerulonephritis with MIg deposits (PGNMID) (n = 13), AL amyloidosis (n = 5), light chain deposition disease (n = 5), light chain proximal tubulopathy (n = 2), and light chain cast nephropathy (n = 1). Second, we conducted a literature review to evaluate the rare non-PGNMID entities. We identified 20 studies describing 29 patients that were added to our cohort (total n = 42). RESULTS: Part 1: Patients' median age was 55 years; 31% were women, and 19% were blacks. Twelve patients (46%) lost their grafts at a median of 8 months after diagnosis. Compared to non-PGNMID, PGNMID patients had lower frequency of detectable paraproteins (31% versus 92%, P = 0.004) and hematologic neoplasms (23% versus 77%, P = 0.02). Within PGNMID group, 6 patients changed their apparent immunofluorescence phenotype between monotypic and polytypic, while all 3 patients with hematologic neoplasms had substructure on electron microscopy. Part 2: Whereas light chain cast nephropathy occurred the earliest and had the worst graft survival, AL amyloidosis occurred the latest and had the best graft survival. CONCLUSIONS: MIgARD in the kidney allograft is associated with poor prognosis. While posttransplant PGNMID can change its apparent clonality by immunofluorescence supporting oligoclonal immune responses, the presence of deposit substructure is an important indicator of underlying hematologic neoplasm. Non-PGNMID are often associated with hematologic neoplasms and varied prognosis.

Environmental and Occupational Exposures in Kidney Disease.

More than 8 million deaths each year are attributed to noncommunicable environmental hazards where people live, work, and play. Physical or chemical hazards may be inhaled, ingested, or absorbed through the skin, affecting all organ systems, including the kidney. Heavy metals, pesticides, and infections are some of the environmental hazards associated with kidney dysfunction and chronic kidney disease. The severity of the effects of these exposures likely is modulated by the timing and duration of exposure, genetic susceptibility, and other conditions, and may lead to the development of acute and/or chronic kidney disease. In this review, we discuss environmental exposures that are associated with kidney dysfunction in animals and human beings, with a focus on those implicated in causing chronic kidney disease.

Relevance of B-Lines on Lung Ultrasound in Volume Overload and Pulmonary Congestion: Clinical Correlations and Outcomes in Patients on Hemodialysis.

BACKGROUND: Volume overload in patients on hemodialysis (HD) is an independent risk factor for cardiovascular mortality. B-lines detected on lung ultrasound (BLUS) assess extravascular lung water. This raises interest in its utility for assessing volume status and cardiovascular outcomes. METHODS: End-stage renal disease patients on HD at the Island Rehab Center being older than 18 years were screened. Patients achieving their dry weight (DW) had a lung ultrasound in a supine position. Scores were classified as mild (0-14), moderate (15-30), and severe (>30) for pulmonary congestion. Patients with more than 60 were further classified as very severe. Patients were followed for cardiac events and death. RESULTS: 81 patients were recruited. 58 were males, with a mean age of 59.7 years. 44 had New York Heart Association (NYHA) class 1, 24 had class 2, and 13 had class 3. In univariate analysis, NYHA class was associated with B-line classes (<0.001) and diastolic dysfunction (0.002). In multivariate analysis, NYHA grade strongly correlated with B-line classification (0.01) but not with heart function (0.95). 71 subjects were followed for a mean duration of 1.19 years. 9 patients died and 20 had an incident cardiac event. A Kaplan-Meier survival analysis demonstrated an interval decrease in survival times in all-cause mortality and cardiac events with increased BLUS scores (p = 0.0049). Multivariate Cox regression analysis showed the independent predictive value of BLUS class for mortality and cardiac events with a heart rate of 2.98 and 7.98 in severe and very severe classes, respectively, compared to patients in the mild class (p = 0.025 and 0.013). CONCLUSION: At DW, BLUS is an independent risk factor for death and cardiovascular events in patients on HD.

Acute kidney injury adjusted to volume status in critically ill patients: recognition of delayed diagnosis, restaging, and associated outcomes.

Critically ill patients receive a significant amount of fluids leading to a positive fluid balance; this dilutes serum creatinine resulting in an overestimated glomerular filtration rate. The goal of our study is to identify undiagnosed or underestimated acute kidney injury (AKI) in the intensive care unit (ICU). It will also identify the morbidity and mortality associated with an underestimated AKI. We reviewed records of patients admitted to our institution (Staten Island University Hospital) between 2012 and 2013 for more than 2 days. Patients with end stage renal disease were excluded. AKI was defined using the Acute Kidney Injury Network criteria. The following formula was used to identify and restage patients with AKI: adjusted creatinine = serum creatinine × [(hospital admission weight (kg) 0.6 + Σ (daily cumulative fluid balance (L))/hospital admission weight × 0.6]. The primary outcome identified newly diagnosed AKI and those who were restaged. The secondary outcome identified associated morbidities. Seven-hundred and thirty-three out of 1,982 ICU records reviewed, were used. Two-hundred and fifty-seven (mean age 69.8±14.9) had AKI, out of which 15.9% were restaged using the equation. Comparison of mean by Student's t-test showed no difference between patients who were restaged. Similarly, chi-square revealed no differences between both arms, except mean admission weight (lower in patients who were restaged), fluid balance on days 1, 2, and 3 (higher in the restaged arm), and the presence of congestive heart failure (more prevalent in the restaged arm). Of note, the mean cost of stay was US$150,562.82 vs $197,174.63 for same stage vs restaged, respectively, however, without statistical significance (P=0.74). Applying the adjustment equation showed a modest (15.9%) increase in the AKI staging slightly impacting outcomes (mortality, length, and cost of stay) without statistical significance.

Immunoglobulin D Multiple Myeloma With Rapidly Progressing Renal Failure.

Immunoglobulin D (IgD) multiple myeloma (MM) is a very rare form of myeloma affecting less than 2% of all myeloma patients. It has a multiorgan involvement with renal failure being the key feature. We present here a case of IgD MM in a 62-year-old white male, smoker with past medical history of hypertension, who presented to emergency department with complaints of lower abdominal pain, constipation and decreased urination. Physical exam was unremarkable. Laboratory investigation showed S.Cr 5.99 mg/dL, hemoglobin 8.7 g/dL and corrected S.Ca 10.6 mg/dL. Urine dipstick showed 100 protein and TP/Cr ratio was 23. Serology was positive for serum free lambda chain level of 8,947.6 mg/L as well with free κ/λ ratio < 0.01. The results of serum and urine electrophoresis and immunofixation were also supportive of diagnosis of IgD MM. IgD level was remarkably elevated (27,300 mg/L) too. CT scan of abdomen/pelvis was negative for obstructive uropathy. Skeletal survey showed a solitary lytic lesion in the iliac crest. His kidney function deteriorated next day requiring hemodialysis. The bone marrow biopsy was positive for plasma cell hypercellularity (70-80%) and flow cytometry showed 8% monoclonal IgD lambda plasma cells. The patient was started on bortezomib and dexamethasone and he underwent bone marrow transplant 6 months later. He is doing well hematologically now but he remains dialysis-dependent. IgD MM is a very rare disease affecting younger population with poor prognosis; patients often end up on hemodialysis despite better control of the hematological component.