CVVHD results in longer filter life than pre-filter CVVH: Results of a quasi-randomized clinical trial.

BACKGROUND: Filter clotting is a major issue in continuous kidney replacement therapy (CKRT) that interrupts treatment, reduces delivered effluent dose, and increases cost of care. While a number of variables are involved in filter life, treatment modality is an understudied factor. We hypothesized that filters in pre-filter continuous venovenous hemofiltration (CVVH) would have shorter lifespans than in continuous venovenous hemodialysis (CVVHD). METHODS: This was a single center, pragmatic, unblinded, quasi-randomized cluster trial conducted in critically ill adult patients with severe acute kidney injury (AKI) at the University of Iowa Hospitals and Clinics (UIHC) between March 2020 and December 2020. Patients were quasi-randomized by time block to receive pre-filter CVVH (convection) or CVVHD (diffusion). The primary outcome was filter life, and secondary outcomes were number of filters used, number of filters reaching 72 hours, and in-hospital mortality. RESULTS: In the intention-to-treat analysis, filter life in pre-filter CVVH was 79% of that observed in CVVHD (mean ratio 0.79, 95% CI 0.65-0.97, p = 0.02). Median filter life (with interquartile range) in pre-filter CVVH was 21.8 (11.4-45.3) and was 26.6 (13.0-63.5) for CVVHD. In addition, 11.8% of filters in pre-filter CVVH were active for >72 hours, versus 21.2% in the CVVHD group. Finally, filter clotting accounted for the loss of 26.7% of filters in the CVVH group compared to 17.5% in the CVVHD group. There were no differences in overall numbers of filters used or mortality between groups. CONCLUSIONS: Among critically patients with severe AKI requiring CKRT, use of pre-filter CVVH resulted in significantly shorter filter life compared to CVVHD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04762524. Registered 02/21/21-Retroactively registered, https://clinicaltrials.gov/ct2/show/NCT04762524?cond=The+Impact+of+CRRT+Modality+on+Filter+Life&draw=2&rank=1.

Kidney Transplantation, Immunosuppression and the Risk of Fracture: Clinical and Economic Implications.

Rationale & Objective: Disorders of bone and mineral metabolism frequently develop with advanced kidney disease, may be exacerbated by immunosuppression after kidney transplantation, and increase the risk of fractures. Study Design: Retrospective database study. Setting & Participants: Kidney-only transplant recipients aged ≥18 years from 2005 to 2016 in the United States captured in US Renal Data System records, which integrate Organ Procurement and Transplantation Network/United Network for Organ Sharing records with Medicare billing claims. Exposures: Various immunosuppression regimens in the first 3 months after kidney transplantation. Outcomes: The development of fractures, as ascertained using diagnostic codes on Medicare billing claims. Analytical Approach: We used multivariable Cox regression with inverse propensity weighting to compare the incidence of fractures >3 months-to-3 years after kidney transplantation associated with various immunosuppression regimens compared to a reference regimen of antithymocyte globulin (TMG) or alemtuzumab (ALEM) with tacrolimus + mycophenolic acid + prednisone using inverse probability treatment weighting. Results: Overall, fractures were identified in 7.5% of kidney transplant recipients (women, 8.8%; men, 6.7%; age < 55 years, 5.9%; age ≥ 55 years, 9.3%). In time-varying regression, experiencing a fracture was associated with a substantially increased risk of subsequent death within 3 months (adjusted hazard ratio [aHR], 3.06; 95% confidence interval [CI], 2.45-3.81). Fractures were also associated with increased Medicare spending (first year: $5,122; second year: $10,890; third year: $11,083; [P < 0.001]). Induction with TMG or ALEM and the avoidance or early withdrawal of steroids significantly reduced the risk of fractures in younger (aHR, 0.63; 95% CI, 0.54-0.73) and older (aHR, 0.83; 95% CI, 0.74-0.94) patients. The avoidance or early withdrawal of steroids with any induction was associated with a reduced risk of fractures in women. Limitations: This was a retrospective study which lacked data on immunosuppression levels. Conclusions: Fractures after kidney transplantation are associated with significantly increased mortality risk and costs. The early avoidance or early withdrawal of steroids after induction with TMG or ALEM reduces the risk of fractures after kidney transplantation and should be considered for patients at high-risk of this complication, including older adults and women.

Severe hypercalcaemia from ectopic intact parathyroid hormone secretion treated with continuous renal replacement therapy in a patient with two malignancies.

We present a 61-year-old Caucasian woman with endometroid carcinoma as well as a poorly differentiated adenocarcinoma who developed severe hypercalcaemia in the setting of an elevated intact parathyroid hormone. The patient was hospitalised twice for her condition. During her first hospitalisation, she was diagnosed with an endometroid carcinoma and hypercalcaemia. With medical management, she had a normal calcium level on discharge. She presented 3 weeks later with hypercalcaemia and encephalopathy. This time her hypercalcaemia was refractory to medical management, and required continuous renal replacement therapy (CRRT) to normalise her serum calcium. Lung biopsy revealed a poorly differentiated adenocarcinoma, suspicious for pancreatic primary. Due to her poor prognosis, rapid elevation of calcium with each attempt to discontinue CRRT, and the poor options for treatment of her cancers, she elected to pursue hospice care.

Using race to estimate glomerular filtration and its impact in kidney transplantation.

Since direct measurement of glomerular filtration rate (GFR) is time-consuming and more expensive, estimated GFR (eGFR) based on measured laboratory values is widely used to determine kidney function. Commonly used formulae to calculate eGFR are dependent on variables, which include filtration markers like serum creatinine and patient characteristics including race. Medical algorithms which utilize race are increasingly being scrutinized, as race is recognized to be a social construct rather than a biologic one. eGFR calculations have important implications for kidney transplantation, both in the listing of candidates as well as in the evaluation of potential kidney donors. This review considers the specific implications of race-based eGFR calculations on recipient evaluation and on decisions related to living kidney donation. We suggest a potential policy solution to ensure that racial and ethnic minority patients are not disadvantaged by eGFR as a result of current calculation methods.

Minimal Change Disease With Nephrotic Syndrome Associated With Coronavirus Disease 2019 After Apolipoprotein L1 Risk Variant Kidney Transplant: A Case Report.

Kidney injury is a well-known complication in people with coronavirus disease 2019 (COVID-19). In kidney transplant recipients with COVID-19, presentation with nephrotic syndrome has not been well described. We report on a 49-year-old black female kidney transplant recipient who presented 25 years after transplant with clinical features of nephrotic syndrome following a diagnosis of COVID-19. Histologic examination showed acute tubular injury with unremarkable glomeruli on light microscopy and diffuse foot process effacement of podocytes on electron microscopy, consistent with minimal change-like podocyte injury. Apolipoprotein L1 (APOL1) genetic testing confirmed 2 high-risk APOL1 alleles in the kidney donor. We speculate that COVID-19-induced systemic or local cytokine release could serve as a second hit in the presence of APOL1 risk alleles and mediate a podocytopathy manifesting as nephrotic syndrome. The presented case with minimal change-like disease, occurring in the context of the donor high-risk APOL1 genotype, extends the spectrum of clinical manifestations in COVID-19-associated nephropathy.

Desensitization strategies: is it worth it?

Preformed donor-specific antibodies (DSAs) limit access to transplantation for thousands of renal transplant patients. While kidney paired donation offers the best strategy for patients with a living donor, for very highly sensitized patients and those without living donors, a strategy of desensitization offers the best hope of transplantation. Removal of DSAs with plasmapheresis, intravenous immunoglobulin and anti-CD20 antibodies can permit successful transplantation. While the clinical outcomes remain inferior to compatible transplant and the costs are significantly greater, when compared with long-term dialysis treatment, these strategies are offer improved survival and are cost-effective given nationally accepted benchmarks.

Loop Diuretics-Analysis of Efficacy Data for the Perioperative Clinician.

HEART FAILURE (HF) is one of the most common causes of hospitalization in the United States. Loop diuretics (LD) are the mainstay of treatment in the management of acute and chronic HF. Although they generally are effective in relieving symptoms and reducing congestion, LD have not been shown to significantly affect morbidity and mortality. The initial decongestion strategy for management of HF is likely to be an LD, with evidence suggesting that an initial "high-dose" strategy either by twice-daily bolus injection or by continuous infusion is likely to be more successful than an initial lower dose in respect to relief of symptoms but at the expense of increased worsening of renal function. This review focuses on the current state of evidence of different strategies related to the use of LD in the treatment of congestive symptoms in critically ill patients and presents a summary of the body of evidence regarding dosages, timing, and different diuretic agents.

BK virus histopathologic disease severity does not predict allograft outcome in renal transplant recipients.

AIMS: BK polyomavirus nephropathy (BKPyVN) is an important cause of allograft failure after renal transplantation. Despite early screening for the virus, allograft loss from BKPyVN is still experienced in up to 14% of all renal transplant recipients. The aim of this study was to investigate the association between BKPyVN histopathologic disease severity and allograft outcome at our center. METHODS: Kidney transplant recipients who had undergone transplantation between 2002 and 2014 with biopsy proven BKPyVN were eligible for this retrospective study. Each biopsy was re-evaluated by a single pathologist blinded to the clinical data and scored according to the Banff criteria for rejection and BKPyVN. Serum creatinine and BK viral load at the time of biopsy diagnosis as well as allograft outcomes to include allograft survival and serum BK viremia resolution were collected for each recipient to determine if BK virus histopathologic disease severity could predict allograft outcome. RESULTS: Twenty cases of BKPyVN were identified from 1031 total renal transplants performed. There was no statistical association between allograft loss and BKPyVN histopathology (p = 0.49). There was also no statistical association between BKPyVN histopathology and BK viral load at the time of biopsy diagnosis (p = 0.38) or serum BK viremia resolution (p = 0.16). CONCLUSIONS: BKPyVN histopathology does not appear to be useful in predicting renal allograft outcome in those recipients diagnosed with BKPyVN which is in contrast to some previously published data.

Small Split Pediatric Kidneys to Expand the Donor Pool: An Analysis of Scientific Registry of Transplant Recipients (SRTR) Data.

BACKGROUND: Increased use of pediatric deceased donor kidneys could enlarge the deceased donor kidney pool. Kidney transplant outcomes from small pediatric donors were compared with those from ideal kidney (IK) and expanded criteria kidney (ECK) donors to understand the optimal use of pediatric donor kidneys. METHODS: Kaplan-Meier analyses compared long-term patient and death-censored graft survival of en bloc kidney (EBK) and split kidney (SpK) transplants from small pediatric donors (aged ≤8 y and weight <30 kg) with those from IK and ECK. Posttransplant serum creatinine) was compared among these cohorts. Deceased donor kidney disposition was determined from small pediatric donors with ≥1 organ transplanted. RESULTS: Patient and death-censored graft survival were similar among recipients of IK, EBK, and SpK transplants, and were superior to those of recipients of ECK. EBK and SpK transplants from donors 5-30 kg had first-year graft loss similar to ECK. Long-term graft survival and serum creatinine with kidneys from SpK donors >10 kg were better than that with ECK donors. About 3901 transplants were performed from 3660 pediatric donors (53% yield). CONCLUSIONS: Pediatric kidneys can augment the kidney donor pool and should not be considered ECK. If 90% of kidneys from donors (aged ≤8 y and weight <30 kg) with ≥1 organ transplanted been used (as SpK when >10 kg) an additional 159 kidney transplants per year could have been performed. Expanding the use of pediatric kidneys should be further explored by the transplant community.

Treatment for presumed BK polyomavirus nephropathy and risk of urinary tract cancers among kidney transplant recipients in the United States.

Recent case series describe detection of BK polyomavirus (BKV) in urinary tract cancers in kidney transplant recipients, suggesting that BKV could contribute to the development of these cancers. We assessed risk for urinary tract cancers in kidney recipients with or without treatment for presumed BKV nephropathy (tBKVN) using data from the United States Transplant Cancer Match Study (2003-2013). Among 55 697 included recipients, 2015 (3.6%) were reported with tBKVN. Relative to the general population, incidence was similarly elevated (approximately 4.5-fold) for kidney cancer in recipients with or without tBKVN, and incidence was not increased in either group for prostate cancer. In contrast, for invasive bladder cancer, incidence was more strongly elevated in recipients with versus without tBKVN (standardized incidence ratios 4.5 vs. 1.7; N = 48 cases), corresponding to an incidence rate ratio (IRR) of 2.9 (95% confidence interval [CI] 1.0-8.2), adjusted for sex, age, transplant year, and use of polyclonal antibody induction. As a result, recipients with tBKVN had borderline increased incidence for all urothelial cancers combined (renal pelvis, ureter, and bladder cancers: adjusted IRR 2.2, 95% CI 0.9-5.4; N = 89 cases). Together with reports describing BKV detection in tumor tissues, these results support an association between BKV and urothelial carcinogenesis among kidney transplant recipients.

BK polyoma virus infection and renal disease in non-renal solid organ transplantation.

BK virus (BKV) is a non-enveloped DNA virus of the polyomaviridae family that causes an interstitial nephritis in immunosuppressed patients. BKV nephropathy is now a leading cause of chronic kidney disease and early allograft failure following kidney transplantation. It is also known to cause renal disease with a progressive decline in kidney function in non-renal solid organ transplant (NRSOT) recipients, although the disease may not be recognized nor its impact appreciated in this patient population. In this report, we review the existing literature to highlight our current understanding of its incidence in NRSOT populations, the approaches to diagnosis and the potential treatment options.

C1q Donor-Specific Antibody Associates with Post-transplant Biopsy Findings in Highly- Sensitized Kidney Transplant Recipients.

Donor-specific anti-human leukocyte antigen antibodies (DSA) are associated with antibody-mediated rejection (AMR) in kidney transplantation, but the spectrum of graft injury seen in patients with DSA ranges from no damage to florid rejection. Since immunoglobulin G (IgG) antibodies with cytotoxic potential can be distinguished by their binding complement fraction C1q, the level of C1q-binding IgG (C1q+) DSA may be useful for stratifying risk or diagnosing AMR. We therefore investigated the value of IgG and C1q+ DSA in predicting pathologic features of AMR on kidney biopsies. We tested the associations between DSA at different cut-off levels and pathologic features of AMR on biopsy in a cohort of consecutive, highly-sensitized patients transplanted after December 2014 who had 1-, 3-, and 6-month protocol kidney biopsies and monitoring for IgG and C1q+ DSA. Eight patients with cPRA >90% and negative flow crossmatch underwent kidney transplant and completed six months of follow-up contributing 23 pairs of biopsy/ serum samples for analysis. C1q+ DSA was significantly associated with C4d finding on biopsy at mean fluorescence intensity (MFI) cut-offs of >100 (p=0.046) and >300 (p=0.008) and showed superior positive and negative predictive value in comparison to conventional IgG DSA. C1q+ DSA also showed significant association and good predictive value for any AMR feature on biopsy (p=0.003, for >100 MFI; p=0.005 for >300 MFI), while IgG DSA showed no association. In a small cohort of high cPRA transplant recipients, C1q+ DSA outperformed IgG DSA as an indicator of AMR biopsy findings. Including C1q+ DSA testing in post-transplant DSA monitoring of highly-sensitized patients may aid the timely diagnosis of AMR.

BK virus in the kidney transplant patient.

BK virus, a member of the polyomavirus family, is a well-recognized cause of irreversible graft failure after kidney transplantation. Awareness of the relationship between BK infection and immunosuppression along with better understanding of its pathogenesis has contributed to increasing rates of its diagnosis. Current therapies are aimed at early diagnosis, limiting inflammation caused by the virus and elimination of the virus through different strategies. The epidemiology, pathogenesis and the different modalities of therapy available are discussed in this review along with the approach to retransplantation in the setting of graft failure from BK infection.

Acute antibody-mediated renal allograft rejection associated with HLA-Cw17 antibody.

Detection of donor-specific human leukocyte antigen (HLA) antibodies is an important part of diagnosis of antibody-mediated rejection (AMR) in the renal transplant population. Donor-specific antibodies (DSA) against HLA-C, a Class 1 major histocompatibility gene product, are not considered to be of major importance in renal transplant rejection. Typing for HLA-C is not a routine part of pre- and post-transplant evaluation. In roughly 10% of biopsy-proven C4d-positive rejections, DSA are not detected by standard testing protocols. In some of these cases, minor HLA and non-HLA antibodies have been implicated. The role of HLA-C antibodies in this patient group is not clear. We present a patient with acute renal graft dysfunction 21 months post-transplant. The allograft biopsy showed features of AMR with diffuse margination of inflammatory cells and diffuse C4d staining in peritubular capillaries. HLA-Cw17 antibody was detected by single-bead antigen Luminex assay, which was further confirmed by a mock flow crossmatch. This case highlights the importance of checking anti-HLA-Cw antibodies in patients with AMR and no detectable DSA using standard methods.

Diffuse infiltrative lymphocytosis syndrome presenting as reversible acute kidney injury associated with Gram-negative bacterial infection in patients with newly diagnosed HIV infection.

Diffuse infiltrative lymphocytosis syndrome (DILS) is believed to be an immunologic syndrome, most likely in response to human immunodeficiency virus (HIV) antigens, and can be accompanied by decreased kidney function. The spectrum of kidney involvement includes acute or chronic kidney disease, primarily tubular proteinuria; enlarged kidneys on imaging studies; and dense lymphocytic tubulointerstitial infiltrates predominantly composed of CD8(+) T cells on kidney biopsy. We describe 3 newly diagnosed HIV-positive patients of African descent with the histologic and clinical diagnosis of DILS who presented with acute kidney injury associated with Gram-negative bacterial infections. Solely with specific antibiotic therapy without antiviral and/or corticosteroid therapy, all patients recovered from acute kidney injury and had partial to complete resolution of proteinuria and enlarged kidney size. These observations led us to hypothesize that an altered immunologic and/or inflammatory response to the endotoxin derived from Gram-negative bacteria, rather than an immunologic response directed to HIV-related antigens, may be a pathogenetic mechanism for the kidney disease associated with DILS in a subset of HIV-positive patients, especially those of immunogenetically susceptible African descent.