Short- and Long-Term Renal Function After Partial Nephrectomy: Comparison of Solitary and Multifocal Renal Masses.

INTRODUCTION: Multifocal partial nephrectomy (MPN) is a critical management strategy for extirpation of multiple distinct renal masses; however, its short- and long-term impact on renal function remains poorly described. Herein we compared absolute glomerular filtration rate (GFR) and change from baseline at multiple time points after MPN and standard partial nephrectomy (SPN). METHODS: Perioperative and pathologic characteristics of 1307 partial nephrectomies performed from 2009 to 2020 were identified. 3:1 propensity score methods were used to match MPN and SPN cohorts based on preoperative characteristics known to impact renal function. Differences in GFR, perioperative outcomes, and overall and recurrence-free survival were assessed. Absolute and relative change from baseline GFR was compared at 5 time points for 36 months after partial nephrectomy. RESULTS: After propensity score matching, 192 SPNs and 64 MPNs with a median GFR of 80.2 mL/min were compared. MPN was associated with a greater decline in GFR of between 11% and 18% for the first year compared to a decline of 7% to 10% for SPN. This difference stabilized after 24 months. However, no differences in overall survival or recurrence-free survival were observed. Median follow-up time was 46.7 months. CONCLUSIONS: Long-term renal function after MPN remains similar to SPN despite greater declines in the first year after excision of multifocal renal masses.

Proteinase 3 Antibody and Anti-Double-Stranded DNA in a Patient With Immunoglobin Light Chain Amyloidosis.

Proteinase 3 (PR3) anti-neutrophil cytoplasmic antibodies (ANCA) and anti-double-stranded DNA (anti-dsDNA) antibodies have been associated with a variety of nephritic diseases, most recognizably granulomatosis with polyangiitis and systemic lupus erythematosus (SLE) glomerulonephritis, respectively. We report the first clinical case of positive PR3 and dsDNA in a patient with renal Immunoglobin light chain (AL) amyloidosis. A 75-year-old man presented to the hospital with chronic fatigue, weight loss, and a recent diagnosis of left ventricular infiltrative cardiomyopathy secondary to AL amyloidosis. Autoimmune serology was significant for PR3-ANCA and anti-dsDNA antibodies. A renal biopsy confirmed AL amyloidosis with diffuse Congo red stain. This case report is the first of its kind, showing atypical antibody presentation in the setting of amyloidosis.

Outcomes of CD19-Targeted Chimeric Antigen Receptor T Cell Therapy for Patients with Reduced Renal Function Including Dialysis.

Patients with renal impairment (RI) are typically excluded from trials evaluating chimeric antigen receptor (CAR) T cell therapies. We evaluated the outcomes of patients with RI receiving standard of care (SOC) CAR T cell therapy for relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this retrospective, single-center cohort study of patients with R/R DLBCL treated with SOC axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) after 2 or more prior lines of therapy, renal and survival outcomes were compared based on RI and fludarabine dose reduction (DR) status. RI was defined by an estimated glomerular filtration rate <60 mL/min/1.73 m2 as determined by the Modification of Diet in Renal Disease equation using day -5 creatinine (Cr) values. Acute kidney injury (AKI) was identified and graded using standard Kidney Disease: Improving Global Outcomes criteria. Renal recovery was considered to occur if Cr was within .2 mg/mL of baseline by day +30. Fludarabine was considered DR if given at <90% of the recommended Food and Drug Administration label dose. Among 166 patients treated with CAR T cell therapy were 17 patients (10.2%) with baseline RI and 149 (89.8%) without RI. After CAR T cell infusion, the incidence of any grade AKI was not significantly different between patients with baseline RI and those without RI (42% versus 21%; P = .08). Similarly, severe grade 2/3 AKI was seen in 1 of 17 patients (5.8%) with baseline RI and in 11 of 149 patients (7.3%) without RI (P = 1). Decreased renal perfusion (28 of 39; 72%) was the most common cause of AKI, with cytokine release syndrome (CRS) contributing to 17 of 39 AKIs (44%). Progression-free survival (PFS) and overall survival (OS) did not differ between patients with RI and those without RI or between those who received standard-dose fludarabine and those who received reduced-dose fludarabine. In contrast, patients with AKI had worse clinical outcomes than those without AKI (multivariable PFS: hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.2 to 3.7; OS: HR, 3.9; 95% CI, 2.1 to 7.4). Notably, peak inflammatory cytokine levels were higher in patients who experienced AKI. Finally, we describe 2 patients with end-stage renal disease (ESRD) on dialysis who received lymphodepletion and CAR T cell therapy. Baseline renal function did not affect renal or efficacy outcomes after CAR T cell therapy in DLBCL. On the other hand, patients with AKI went on to experience worse clinical outcomes. AKI was commonly related to CRS and high peak inflammatory cytokine levels. CAR T cell therapy is feasible in patients with ESRD and requires careful planning of lymphodepletion.

A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant.

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.

A Case of Diffuse and Nodular Glomerulosclerosis in Waldenstrom's Macroglobulinemia.

Diffuse and nodular glomerulosclerosis is associated with diabetic nephropathy and occasionally with tobacco users. However, it has also been linked with amyloidosis, cryoglobulinemia, and light-chain deposition disease. To the best of our knowledge, there is no published data on diffuse and nodular glomerulosclerosis without light chain deposition in Waldenstrom's macroglobulinemia (WM). We present a case of diffuse and nodular glomerulosclerosis in a non-diabetic, non-smoker with WM.

Emerging Concepts in Hematopoietic Stem Cell Transplantation-Associated Renal Thrombotic Microangiopathy and Prospects for New Treatments.

Thrombotic microangiopathy associated with hematopoietic stem cell transplantation (HSCT-TMA) is a well-recognized complication of HSCT that has a high risk for death. Even in patients who survive, HSCT-TMA is associated with long-term morbidity and chronic organ injury. HSCT-TMA is a multisystem disease that often affects the kidneys. Renal manifestations of HSCT-TMA include reduced glomerular filtration rate, proteinuria, and hypertension. Understanding of the pathophysiology of HSCT-TMA has expanded in the last decade. Endothelial injury plays a major role. Recent studies also suggest involvement of complement activation. HSCT-TMA has also been considered by some to be an endothelial variant of graft-versus-host disease. Understanding the pathophysiology of HSCT-TMA and its association with activation of the complement system may aid in developing novel therapeutic options. In this review, we summarize current knowledge focusing on epidemiology and prognosis, evidence of complement activation, and endothelial injury; the possible link to graft-versus-host disease; and treatment options for HSCT-TMA.

Renal Function and Outcomes With Use of Left Ventricular Assist Device Implantation and Inotropes in End-Stage Heart Failure: A Retrospective Single Center Study.

BACKGROUND: Left ventricular assist device (LVAD) and inotrope therapy serve as a bridge to transplant (BTT) or as destination therapy in patients who are not heart transplant candidates. End-stage heart failure patients often have impaired renal function, and renal outcomes after LVAD therapy versus inotrope therapy have not been evaluated. METHODS: In this study, 169 patients with continuous flow LVAD therapy and 20 patients with continuous intravenous inotrope therapy were analyzed. The two groups were evaluated at baseline and at 3 and 6 months after LVAD or inotrope therapy was started. The incidence of acute kidney injury (AKI), need for renal replacement therapy (RRT), BTT rate, and mortality for 6 months following LVAD or inotrope therapy were studied. Results between the groups were compared using Mann-Whitney U test and Chi-square with continuity correction or Fischer's exact at the significance level of 0.05. RESULTS: Mean glomerular filtration rate (GFR) was not statistically different between the two groups, with P = 0.471, 0.429, and 0.847 at baseline, 3 and 6 months, respectively. The incidence of AKI, RRT, and BTT was not statistically different. Mortality was less in the inotrope group (P < 0.001). CONCLUSION: Intravenous inotrope therapy in end-stage heart failure patients is non-inferior for mortality, incidence of AKI, need for RRT, and renal function for 6-month follow-up when compared to LVAD therapy. Further studies are needed to compare the effectiveness of inotropes versus LVAD implantation on renal function and outcomes over a longer time period.

Thrombotic Microangiopathy With Granulomatosis Interstitial Nephritis in an Allogenic Bone Marrow Transplant Patient: A Case Report and Review of the Literature.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare complication of hematopoietic stem cell transplantation (HSCT) with variable presentations. TA-TMA has often been described as a diagnosis of exclusion but a renal biopsy is rarely pursued to confirm the diagnosis, an essential step for our patient with renally limited TMA. We report a case report from the onconephrology clinic and review the literature associated with TA-TMA as it relates to diagnosis and treatment. A 45-year-old woman with acute myeloid leukemia and stage 3 chronic kidney disease underwent a matched unrelated donor allogenic HSCT. Postoperatively, she developed gastrointestinal graft versus host disease (GvHD) and was treated with tacrolimus, sirolimus, budesonide, and beclomethasone. Following discharge, she developed uncontrolled hypertension and required losartan, amlodipine, carvedilol, clonidine patch, and hydralazine as needed. On day 180 post-transplant, she developed lower extremity edema and acute kidney injury (AKI) with creatinine increasing to 2 mg/dL. On day 480 post-transplant, she developed worsening thrombocytopenia, anemia, new hematuria, left flank pain, and worsening renal function with creatinine peaking to 6 mg/dL. Peripheral smear revealed no schistocytes, lactate dehydrogenase of 265 mg/dL, and urinalysis with 100 mg/dL protein. ADAMTS 13 activity was normal (92%) and no inhibitor was detected. She became anuric and was started on hemodialysis. Renal biopsy revealed glomerular changes consistent with TA-TMA. During HSCT, systemic vascular endothelial injury triggers microangiopathic hemolytic anemia, platelet consumption, injury of glomerular endothelial cells and fibrin occluded renal capillaries. Thus, TA-TMA should be considered in HSCT patients with elevated LDH, proteinuria, hypertension, and AKI. However, a diagnosis is difficult to confirm without a renal biopsy. Treatment involves discontinuing potentially toxic agents such as calcineurin inhibitors and sirolimus, prescribing adequate antimicrobial treatment, and using renal replacement therapy if needed. A renal biopsy early in the course of disease not only confirms the diagnosis, but may limit the extent of disease.

The impact of reporting estimated glomerular filtration rate.

The 'Kidney Disease Outcomes Quality Initiative' guidelines recommend laboratory reporting of a calculated estimated glomerular filtration rate (eGFR). The United Kingdom and several states already mandate reporting eGFR for every laboratory serum creatinine (sCr) measurement. In our study, we evaluated the impact of reporting eGFR on the management of hospitalized patients. We reviewed the medical records for 2000 patients, 1000 pre- and 1000 post-reporting eGFR. We excluded patients with previous diagnosis of chronic kidney disease, acute kidney failure, and end-stage renal disease. We analyzed the subgroup of patients with eGFR <60 and sCr <1.5 mg/dL. We did not notice an increase in the number of renal consult, ordering laboratory or imaging study to evaluate chronic kidney disease. The prescription habits did not change for nephrotoxic medications (nonsteroidal anti-inflammatory drugs and aminoglycosides). We did not find any change in the percentage of patients who received hydration for a radiological contrast study or the use of N-acetylcysteine. In conclusion, reporting eGFR did not improve the renal management of hospitalized patients.

Effects of parathyroid hormone on immune function.

Parathyroid hormone (PTH) function as immunologic mediator has become interesting with the recent usage of PTH analogue (teriparatide) in the management of osteoporosis. Since the early 1980s, PTH receptors were found on most immunologic cells (neutrophils, B and T cells). The in vitro evaluations for a possible role of PTH as immunomodulator have shown inconsistent results mainly due to methodological heterogeneity of these studies: it used different PTH formulations (rat, bovine, and human), at different dosages and different incubating periods. In some of these studies, the lymphocytes were collected from uremic patients or animals, which renders the interpretation of the results problematic due to the effect of uremic toxins. Parathyroidectomy has been found to reverse the immunologic defect in patients with high PTH levels. Nonetheless, the clinical significance of these findings is unclear. Further studies are needed to define if PTH does have immunomodulatory effects.