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In addition to their fundamental role in clearance, the kidneys release select molecules into the circulation, but whether any of these anabolic functions provides insight on kidney health is unknown. Using aptamer-based proteomics, we characterized arterial (A)-to-renal venous (V) gradients for >1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that changed significantly decreased from A to V, consistent with renal clearance, several were found to increase, the most significant of which was testican-2. To assess the clinical implications of these physiologic findings, we examined proteomic data in the Jackson Heart Study (JHS), an African-American cohort (n = 1,928), with replication in the Framingham Heart Study (FHS), a White cohort (n = 1,621). In both populations, testican-2 had a strong, positive correlation with estimated glomerular filtration rate (eGFR). In addition, higher baseline testican-2 levels were associated with a lower rate of eGFR decline in models adjusted for age, gender, hypertension, type 2 diabetes, body mass index, baseline eGFR, and albuminuria. Glomerular expression of testican-2 in human kidneys was demonstrated by immunohistochemistry, immunofluorescence, and electron microscopy, while single-cell RNA sequencing of human kidneys showed expression of the cognate gene, SPOCK2, exclusively in podocytes. In vitro, testican-2 increased glomerular endothelial tube formation and motility, raising the possibility that its secretion has a functional role within the glomerulus. Taken together, our findings identify testican-2 as a podocyte-derived biomarker of kidney health and prognosis.

Background: Recent evidence suggests IL-17 contributes to the pathogenesis of autoimmune, inflammatory, and cardiovascular diseases. It has been demonstrated in vivo that IL-17 is critical for the maintenance of angiotensin II-induced hypertension (HTN) and vascular dysfunction. We aim to determine if IL-17 inhibitors (IL-17I) have direct effects on blood pressure (BP) in human subjects. Method: We conducted a single-center retrospective cohort study of patients who had been treated with an IL-17I (ixekuzumab or secukinumab) for psoriasis (P) or psoriatic arthritis (PA). Aggregated data in a 3 month window at 3-months prior to initiation of the IL-17I (baseline) and at 3, 6, and 12 months after initiation were analyzed using paired t-test. Wilcoxon non-parametric test was used if normality test failed. Pre-existing HTN was defined by ICD-coding. Unique antihypertensive medication was defined as number of unique class of BP prescription filled within a specified 3-month windows. Results: We identified 307 patients who had been treated with IL-17I. We included 103 patients who had BP data in all above specified time windows. The mean age was 47 ± 13 years, 39 (38%) were men, 68 (66%) had HTN, and 23 (22%) had diabetes. Among all patients, mean baseline BP was 129/76 mmHg. There was no significant change in systolic or diastolic BP (SBP or DBP, respectively) at 3 months (129/76 mmHg) or 6 months (130/76 mmHg). There was a trend of increased BP at 12 months (131/77 mm Hg), reaching significance only for DBP (p = 0.048). When stratified by pre-existing HTN, there was no significant change in SBP or DBP at any time point. The number of unique prescribed BP medication was 0.45 at baseline, and significantly increased to 0.68 (p= 0.027), 0.87 (p=0.006), and 0.83(p=0.004) at 3-,6-, and 12-month respectively, suggesting patients required more antihypertensive therapy while on IL-17I. Conclusion: IL-17I use for P or PA was not associated with a significant change in BP over 1 year of treatment. This could be confounded by an increase in the number of unique BP medications prescribed which implies a rise in BP. This could be due to IL-17I therapy or other factors such as age. A prospective study is needed to better evaluate the effects of IL-17 inhibition on BP.

Hyperkalemia refers to an elevated serum potassium level (usually >5.5 mEq/L). Severe hyperkalemia defined as serum potassium >6.5 mEq/L or 5.6–6.4 mEq/L with symptoms or EKG changes requires immediate treatment. Initial treatment with calcium gluconate will stabilize the cardiac myocyte membrane, while other therapies such as insulin and beta agonists promote intracellular uptake. For patients with normal or moderately reduced renal function, loop diuretics and gastrointestinal binding resins may be used to eliminate potassium. In the presence of advanced renal failure, or when conservative therapies fail, hemodialysis is needed and nephrology consultation must be ordered. A thorough investigation into the causes of the hyperkalemia will help to tailor further treatment. Assess for high potassium intake, release from intracellular stores (acidosis or cell injury), and impaired potassium excretion (renal failure or impaired aldosterone action).

Alport syndrome is a hereditary disease affecting Type IV collagen characterized by hematuria, progressive renal failure, sensorineural hearing loss, and ocular abnormalities. Most cases are X-linked and involve the COL4A5 gene with a minority of patients having autosomal recessive mutations in the COL4A3 or COL4A4 genes encoding the α3(IV) or α4(IV) chain respectively. Here, we describe the case of a 31-year-old woman who presented during pregnancy with hematuria and proteinuria and was diagnosed with autosomal recessive Alport syndrome (ARAS) post-partum. Her biopsy was notable for findings of segmental glomerulosclerosis with some collapsing features, in addition to thin basement membranes and rare “splitting”. Genetic testing identified 2 novel mutations in the COL4A4 gene: a truncating frame shift mutation c.3861delinsCTC and a missense mutation c.4708G>A (p.Glu1570Lys), both of which we assert to be pathogenic. She had normal full-term delivery without complications. This case has several unique features including the relatively mild disease phenotype and the findings of glomerular scarring with collapsing features on renal biopsy. The successful pregnancy outcome and her clinical presentation add to the growing body of evidence that ARAS can have a variable phenotype.

Background: Delayed renal graft function (DGF) contributes to the determination of length of hospitalization, risk of acute rejection, and graft loss. Existing tools aid the diagnosis of specific DGF etiologies such as antibody-mediated rejection, but markers of recovery have been elusive. The peroxisome proliferator gamma co-activator-1-alpha (PGC1α) is highly expressed in the renal tubule, regulates mitochondrial biogenesis, and promotes recovery from experimental acute kidney injury. Objectives: We aimed to determine the association between renal allograft PGC1α expression and recovery from delayed graft function. Methods: We retrospectively analyzed patients undergoing renal transplantation at a single center from January 1, 2008 to June 30, 2014. PGC1α expression was assessed by immunostaining and ultrastructural characteristics by transmission electron microscopy. Of 34 patients who underwent renal biopsy for DGF within 30 days of transplant, 21 were included for analysis. Results: Low PGC1α expression was associated with a significantly longer time on dialysis after transplant (median of 35.5 vs. 16 days, p < 0.05) and a significantly higher serum creatinine (sCr) at 4 weeks after transplantation among those who discontinued dialysis (5 vs. 1.65 mg/dL, p < 0.0001). Low PGC1α expression was not associated with higher sCr at 12 weeks after transplantation. Ultrastructural characteristics including apical membrane blebbing and necrotic luminal debris were not informative regarding clinical outcomes. Conclusions: These data suggest that higher PGC1α expression is associated with faster and more complete recovery from DGF. Mitochondrial biogenesis may be a therapeutic target for DGF. Larger studies are needed to validate these findings.