The evolution of performing a kidney biopsy: a single center experience comparing native and transplant kidney biopsies performed by interventional radiologists and nephrologists.

BACKGROUND: Kidney biopsy is the most vital tool guiding a nephrologist in diagnosis and treatment of kidney disease. Over the last few years, we have seen an increasing number of kidney biopsies being performed by interventional radiologists. The goal of our study was to compare the adequacy and complication rates between kidney biopsies performed by interventional radiology versus nephrology.  METHODS : We performed a single center retrospective analysis of a total of all kidney biopsies performed at our Institution between 2015 and 2021. All biopsies were performed using real-time ultrasound. Patients were monitored for four hours post biopsy and repeat ultrasound or hemoglobin checks were done if clinically indicated. The entire cohort was divided into two groups (Interventional radiology (IR) vs nephrology) based on who performed the biopsy. Baseline characteristics, comorbidities, blood counts, blood pressure, adequacy of the biopsy specimen and complication rates were recorded. Multivariable logistic regression was used to compare complication rates (microscopic hematuria, gross hematuria and need for blood transfusion combined) between these two groups, controlling for covariates of interest. ANCOVA (analysis of variance, controlling for covariates) was used to compare differences in biopsy adequacy (number of glomeruli per biopsy procedure) between the groups. RESULTS: 446 kidney biopsies were performed in the study period (229 native and 147 transplant kidney biopsies) of which 324 were performed by IR and 122 by nephrologist. There was a significantly greater number of core samples obtained by IR (mean = 3.59, std.dev. = 1.49) compared to nephrology (mean = 2.47, std.dev = 0.79), p < 0.0001. IR used 18-gauge biopsy needles while nephrologist exclusively used 16-gauge needles. IR used moderate sedation (95.99%) or general anesthesia (1.85%) for the procedures more often than nephrology, which used them only in 0.82% and 0.82% of cases respectively (p < 0.0001). Trainees (residents or fellows) participated in the biopsy procedures more often in nephrology compared to IR (97.4% versus 69.04%, p < 0.0001). The most frequent complication identified was microscopic hematuria which occurred in 6.8% of biopsies. For native biopsies only, there was no significant difference in likelihood of complication between groups, after adjustment for covariates of interest (OR = 1.01, C.I. = (0.42, 2.41), p = 0.99). For native biopsies only, there was no significant difference in mean number of glomeruli obtained per biopsy procedure between groups, after adjustment for covariates of interest (F(1,251) = 0.40, p = 0.53). CONCLUSION: Our results suggest that there is no significant difference in the adequacy or complication rates between kidney biopsies performed by IR or nephrology. This conclusion may indicate that kidney biopsies can be performed safely with adequate results either by IR or nephrologists depending on each institution's resources and expertise.

Paxlovid (Nirmatelvir/Ritonavir) and Tacrolimus Drug-Drug Interaction in a Kidney Transplant Patient with SARS-2-CoV infection: A Case Report.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a significant impact on communities and health systems. New antiviral medications against this disease have not been properly tested yet, and their efficiency, side effects, and drug-drug interactions are not entirely known. Organ transplant recipients receive immunosuppressive medications such as tacrolimus to prevent graft rejection. Tacrolimus is metabolized by the cytochrome P450 3A4 enzyme system. Many medications can either induce or inhibit this enzyme and affect the level. Awareness of possible drug-drug interactions is vital because tacrolimus levels should be kept within a specific narrow range determined by the recipient's immunologic risk. Underexposure increases the risk of graft rejection, whereas overexposure may lead to adverse effects. Paxlovid, a novel antiviral medication approved for emergency use to treat SARS-CoV-2, is a combination of nirmatrelvir and ritonavir, a cytochrome P450 34A inhibitor. In this case report, we present a case of a kidney transplant patient receiving tacrolimus treated with Paxlovid, leading to an abruptly high tacrolimus level, significant symptoms, treatment interruption, and acute kidney injury. We conclude that the drug-drug interaction between Paxlovid and tacrolimus is indeed robust and noteworthy and leads to high tacrolimus levels and its metabolites, adverse effects, and acute kidney injury. Physicians managing immunocompromised patients receiving tacrolimus should be aware of this significant drug-drug interaction and consider other options or reduction of daily tacrolimus dose during treatment in addition to timely monitoring of both tacrolimus levels and serum creatinine. Consulting with the transplant pharmacist is foremost in alerting for these interactions.

Impact of age mismatch between donor and recipient on heart transplant mortality.

The effect of donor-to-recipient (D-R) age mismatch in adult heart transplant population is not clearly described, and we undertook this study to determine the impact of age mismatch on mortality. Heart transplant recipients from 2000 to 2017 were identified using the United Network of Organ Sharing database. The cohort was divided into three groups: donor age within 5 years of recipient age (Group 1), donors >5 years younger than recipient (group 2), and donors >5 years older than recipients (Group 3). We also evaluated if this finding changed by recipient age. Twenty eight thousand, four hundred and eleven patients met the inclusion criteria. Compared to group 1, the adjusted hazard ratio (aHR) for mortality for group 2 was 0.91 (0.83-0.99, p value <.039) and for group 3 was 1.36 (1.21-1.52, p value <.001); however, when looking at recipient age as continuous variable, receiving a younger heart was protective only for recipients younger than 45 years of age, and receiving a heart transplant from an older donor was detrimental only in recipients aged 25-35.

Proton Pump Inhibitor-Induced Galactorrhea in a Kidney Transplant Recipient: A Friend or Foe?

Over the last decades, proton pump inhibitors (PPIs) have been widely used as the mainstay for treatment and prevention of gastrointestinal side effects, gastroesophageal reflux, and peptic ulcer disease. However, their safety profile has come into question recently after reports relating them to several side effects as well as kidney disease. Omeprazole, one of the mainly used PPIs, is almost entirely metabolized by the liver but the resulting metabolites are renally excreted. These metabolites may inhibit cytochrome P450 2C19 (CYP2C19) and cytochrome P450 3A4 (CYP3A4) reversibly, but as recent evidence suggests, they may also be involved in causing kidney disease. In the setting of renal dysfunction, these metabolites will not be excreted from the body and will accumulate further causing kidney damage and inhibiting CYP enzymes to a greater extent. Abnormally high serum prolactin levels leading to galactorrhea may be the result of such an accumulation. To our knowledge, there have been only three previously reported cases of PPI-induced galactorrhea in the literature but none in a kidney transplant recipient. In patients with established kidney disease and reduced glomerular filtration rate like kidney transplant recipients, the use of PPIs should be thoroughly assessed. Reduced clearance of their metabolites may lead to progression of the kidney disease and lead to more unwanted side effects. We present a case of a female kidney transplant recipient with worsening allograft function who presented with sudden galactorrhea and hyperprolactinemia while on a high-dose omeprazole for gastroesophageal reflux disease.

Frequency of COL4A3/COL4A4 mutations amongst families segregating glomerular microscopic hematuria and evidence for activation of the unfolded protein response. Focal and segmental glomerulosclerosis is a frequent development during ageing.

Familial glomerular hematuria(s) comprise a genetically heterogeneous group of conditions which include Alport Syndrome (AS) and thin basement membrane nephropathy (TBMN). Here we investigated 57 Greek-Cypriot families presenting glomerular microscopic hematuria (GMH), with or without proteinuria or chronic kidney function decline, but excluded classical AS. We specifically searched the COL4A3/A4 genes and identified 8 heterozygous mutations in 16 families (28,1%). Eight non-related families featured the founder mutation COL4A3-p.(G1334E). Renal biopsies from 8 patients showed TBMN and focal segmental glomerulosclerosis (FSGS). Ten patients (11.5%) reached end-stage kidney disease (ESKD) at ages ranging from 37-69-yo (mean 50,1-yo). Next generation sequencing of the patients who progressed to ESKD failed to reveal a second mutation in any of the COL4A3/A4/A5 genes, supporting that true heterozygosity for COL4A3/A4 mutations predisposes to CRF/ESKD. Although this could be viewed as a milder and late-onset form of autosomal dominant AS, we had no evidence of ultrastructural features or extrarenal manifestations that would justify this diagnosis. Functional studies in cultured podocytes transfected with wild type or mutant COL4A3 chains showed retention of mutant collagens and differential activation of the unfolded protein response (UPR) cascade. This signifies the potential role of the UPR cascade in modulating the final phenotype in patients with collagen IV nephropathies.

Four cases of nafcillin-associated acute interstitial nephritis in one institution.

BACKGROUND: Over the course of 1 year, four patients in a single institution developed acute kidney injury most likely secondary to nafcillin-associated acute interstitial nephritis, indicating that this complication might not be as rare as is commonly believed. The main case presented here is that of a 73-year-old man with a history of chronic low back pain who presented with worsening back pain, as well as nausea, vomiting and volume depletion. Imaging studies revealed a soft tissue abscess in the left psoas major muscle. INVESTIGATIONS: Physical examination, complete urine analysis, blood and urine cultures, measurement of peripheral eosinophil and plasma creatinine levels, and renal ultrasound. DIAGNOSIS: Nafcillin-associated acute interstitial nephritis. MANAGEMENT: Discontinuation of nafcillin and provision of supportive care.