Management of Hypertension in Diabetic Kidney Disease.

Hypertension is a critical component of cardiovascular disease progression in patients with chronic kidney disease, and specifically diabetic kidney disease (DKD). Causation versus correlation remains up for debate, but what has been confirmed is the delay of DKD progression when hypertension is controlled or moved to guideline drive ranges. Many medications have been studied and used in real world experience for best outcomes, and we discuss below the proven winners thus far making up the renin angiotensin aldosterone system. As well, we discuss guideline changing medications including sodium-glucose cotransporter 2 inhibitors and newer generation mineralocorticoid receptor antagonists. With the growing prevalence of diabetes and DKD in the population, newer agents are emerging in multiple drug class and will be highlighted below. Clinicians continue to search for the optimal care plans for this challenging patient population.

Incidence and outcomes of acute kidney injury including hepatorenal syndrome in hospitalized patients with cirrhosis in the US.

BACKGROUND & AIMS: Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis. METHODS: We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other). RESULTS: A total of 2,063 patients were included (median age 62 [IQR 54-69] years, 38.3% female, median MELD-Na score 26 [19-31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p <0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p = 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p <0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p <0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p <0.001 for all). CONCLUSION: AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed. IMPACT AND IMPLICATIONS: Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US.

Water Loading and Uromodulin Secretion in Healthy Individuals and Idiopathic Calcium Stone Formers.

BACKGROUND: Uromodulin is a protein made only by the kidney and released in urine, circulating in polymerizing and nonpolymerizing forms. This protein's multiple functions include inhibition of stone formation in the urine. The physiological determinants of uromodulin production are incompletely understood. METHODS: We investigated changes in uromodulin levels and key factors governing its production and release in urine and serum. We performed an experiment to determine whether water loading, a common intervention to prevent stone formation, will alter the rate of uromodulin production. During a 2-day period, 17 stone forming participants and 14 control participants were subjected to water loading (day 1) and normal fluid intake (day 2). Uromodulin levels were measured on timed hourly collections in urine and plasma during the period of the study. RESULTS: Water loading increased urinary uromodulin secretion (33±4 versus 10±4 µ g/min at baseline, P < 0.0001) in stone formers and control participants. Despite high urine volumes, most participants maintained relatively stable urinary uromodulin concentrations. Native Western blots for polymerizing and nonpolymerizing uromodulin suggest that polymerizing uromodulin was the predominant form at higher urinary flow volumes. Urine flow rates and sodium excretion were significant correlates of urinary uromodulin production. Water loading did not affect serum uromodulin levels, which were also not associated with urinary uromodulin. CONCLUSIONS: Water loading increases the secretion of polymerizing urinary uromodulin. This increased secretion reduces the variability of urinary uromodulin concentrations despite high urine volumes. Serum uromodulin levels were not affected by this treatment.

Empagliflozin in Adults with Chronic Kidney Disease (CKD): Current Evidence and Place in Therapy.

Chronic kidney disease guidelines and disease modifying therapy have seen a dramatic shift in the last 5 years. The SGLT2 inhibitor class of medications has been catapulted from hyperglycemia management medications, to cardiovascular and kidney disease improvement therapies. Multiple trials looking at dedicated cardiovascular and kidney endpoints have resulted in favorable results. This review will target empagliflozin and the exciting journey that it has taken along this path. Empagliflozin has been studied for hyperglycemia, cardiovascular, and kidney hard outcome endpoints. Both patients with diabetes and without have been rigorously studied and shown surprising results. The major implications for patients on empagliflozin will be shown. Future studies and directions are highly anticipated to add to the growing knowledge of the SGLT2 inhibitor class, as well as discover possibilities for new disease states to benefit from empagliflozin.

Incidence and Importance of Calcium Deposition in Kidney Biopsy Specimens.

INTRODUCTION: Calcification on native kidney biopsy specimens is often noted by pathologists, but the consequence is unknown. METHODS: We searched the pathology reports in the Biopsy Biobank Cohort of Indiana for native biopsy specimens with calcification. RESULTS: Of the 4,364 specimens, 416 (9.8%) had calcification. We compared clinical and histopathology findings in those with calcification (n = 429) compared to those without calcification (n = 3,936). Patients with calcification were older, had more comorbidities, lower estimated glomerular filtration rates (eGFR), were more likely to have hyaline arteriosclerosis, interstitial fibrosis/tubular atrophy, and a primary pathologic diagnosis of acute tubular injury or acute tubular necrosis when compared to patients without calcification. Patients with calcium oxalate deposition alone, compared to calcium phosphate or mixed calcifications, had fewer comorbidities but were more likely to have a history of gastric bypass surgery or malabsorption and take vitamin D. In patients with two or more years of follow-up, multivariate analyses showed the presence of calcification (HR 0.59, 0.38-0.92, p = 0.02) and higher eGFR (HR 0.76, 0.73-0.79, p < 0.001), was associated with decreased likelihood of progressing to end-stage renal disease. The presence of calcification was also associated with a reduced slope/decline in eGFR compared to known biopsy and clinical risk factors for decline in kidney function. We hypothesized this was due to more recoverable acute kidney injury (AKI) and found more severe acute kidney injury network stage in patients with kidney calcification but also greater improvement over time. DISCUSSION/CONCLUSION: In summary, we demonstrated that calcification on kidney biopsy specimens was associated with a better prognosis than those without calcification due to the association with recoverable AKI.

Update and review of contrast-associated acute kidney injury.

Contrast associated acute kidney injury (CA-AKI) is a controversial subject in the field of nephrology, cardiology, radiology and hospital medicine. Much has been written and published concerning the causes, risk factors, outcomes, and potential treatments to avoid the ultimate outcome of complete kidney failure requiring dialysis. Over the decades many proposed preventative strategies and treatments have failed to produce a reliable outcome. Additionally, there is now a growing discussion of the severity and sincerity of CA-AKI being a major entity to worry about for patients. We discuss the present state of CA-AKI and highlight potential risk factors and possible therapeutic interventions to minimize any impact a contrast procedure may have on a patient in order to maximize the medical care.

Ventricular Assist Devices and Chronic Kidney Replacement Therapy: Technology and Outcomes.

Heart failure and kidney failure are very common conditions, precipitating and exacerbating each other. Left ventricular assist devices (LVADs) represent a relatively new technology for treatment of advanced heart failure. Kidney dysfunction, if present, makes candidate selection for LVADs challenging and contributes to multiple complications while the patients are on an LVAD support. Although kidney function generally improves after LVAD implantation, some patients develop acute and then chronic kidney disease sometimes requiring kidney replacement therapies (KRTs). Overall, chronic KRT in LVAD recipients is feasible and well tolerated, but routine technique of blood pressure monitoring should be adjusted to the continuous blood flow. Both hemodialysis and peritoneal dialysis can be used. Unique challenges for chronic KRT posed by the presence of LVAD are discussed in this review.

Disruption of bone development and homeostasis by trisomy in Ts65Dn Down syndrome mice.

Down syndrome (DS) is a genetic disorder resulting from trisomy 21 that causes cognitive impairment, low muscle tone and craniofacial alterations. Morphometric studies of the craniofacial and appendicular skeleton in individuals with DS suggest that bone development and homeostasis are affected by trisomy. The Ts65Dn mouse model has three copies of approximately half the genes found on human chromosome 21 and exhibits craniofacial skeletal and size differences similar to those observed in humans with DS. We hypothesized that Ts65Dn and euploid mice have distinct differences in bone development and homeostasis influencing both the craniofacial and appendicular skeletal phenotypes. Quantitative assessment of structural and mechanical properties of the femur in Ts65Dn and control mice at 6 and 16 weeks of age revealed significant deficiencies in trabecular and cortical bone architecture, bone mineral density, bone formation, and bone strength in trisomic bone. Furthermore, bone mineral density and dynamic dentin formation rate of the skull and incisor, respectively, were also reduced in Ts65Dn mice, demonstrating that trisomy significantly affects both the craniofacial and appendicular skeleton.