Danniele G. Holanda

COVID-19 (from SARS-CoV-2) is the cause of an ongoing pandemic, with an increasing number of cases and significant mortality worldwide. Clinical trials and extensive studies are being conducted on a large scale for a better understanding of the pathophysiology of this disease and its effect on different organs. Several experimental treatment protocols have been introduced, in which hydroxychloroquine (HCQ) was one of the first drugs used. While patients can develop many side effects of HCQ, studies have documented a rare association of long-term HCQ treatment with zebra-like bodies in the ultrastructural examination of kidney biopsies, a finding typically seen in Fabry’s disease, as well as in association with chronic HCQ use, among other drugs. We present a similar finding in the postmortem examination of a male in his early seventies with COVID-19 infection, who received five days of HCQ treatment before stopping the medication due to cardiac and renal toxicity.

PRKAG2 syndrome (PS) is a rare, early-onset autosomal dominant inherited disease caused by mutations in PRKAG2, the gene encoding the regulatory γ2 subunit of adenosine monophosphate-activated protein kinase. PRKAG2 syndrome is associated with many cardiac manifestations, including pre-excitation, arrhythmias, left ventricular hypertrophy, and chronotropic incompetence frequently leading to early pacemaker placement. A meta-analysis of genome-wide association data in subjects with chronic kidney disease (CKD) identified a susceptibility locus in an intron of PRKAG2, which has been replicated in other studies. However, CKD has not been reported in patients with PS or mutations in PRKAG2. We report a case of a woman diagnosed at age 27 with PS when she presented with atrial fibrillation and pre-excitation on electrocardiogram. By age 35, she had developed mild renal insufficiency and a biopsy demonstrated IgA nephropathy (IGAN). This is the first reported case of IGAN in a patient with PS. We discuss both PS and IGAN and the potential mechanisms by which they could be related.

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 (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.

The purpose of this study was to clarify the association between CT findings and Fuhrman grade of clear cell renal cell carcinoma (ccRCC). The study group consisted of 214 surgically proven ccRCC in 214 patients. Contrast-enhanced CT studies were retrospectively assessed for tumor size, cystic versus solid, calcification, heterogeneity of lesions, percentage of non-enhancing (necrotic) areas, and growth pattern. CT findings and Fuhrman grade were compared. Nineteen of 22 (86.4%) cystic ccRCC were low grade (Fuhrman grades 1-2). There was no significant correlation between tumor size and grade in cystic ccRCC (P = 0.43). In predominantly solid ccRCC, there was significant correlation between tumor size and grade (P < 0.0001). Thirty-eight of 43 (88.4%) infiltrative ccRCC were high grade (Fuhrman grades 3-4). Logistic regression showed tumor size and infiltrative growth were significantly associated with grades 3-4 (P = 0.00083 and P = 0.0059). Cystic ccRCC tends to be low grade. Infiltrative growth and larger tumor size may increase the likelihood of high grade ccRCC.