Acute Kidney Injury

Acute kidney injury (AKI), previously named acute renal failure, is characterized by abrupt deterioration in renal function. The incidence of AKI has increased lately, both in the hospital and community setting. It is estimated that more than 13 million people are affected by AKI annually worldwide. Despite all the advances in the field, AKI still carries a high mortality rate. In addition to mortality, AKI is an important risk factor for the development of chronic kidney disease. In this chapter, various aspects of AKI will be discussed including definition and staging, etiology, pathophysiology, clinical presentation, diagnosis, management, prognosis, and prevention

Risk Factors for Bronchiolitis Obliterans Syndrome after Initial Detection of Pulmonary Impairment after Hematopoietic Cell Transplantation

Pulmonary chronic graft-versus-host-disease (cGVHD), or bronchiolitis obliterans syndrome (BOS), is a highly morbid complication of hematopoietic cell transplantation (HCT). The clinical significance of a single instance of pulmonary decline not meeting the criteria for BOS is unclear. We conducted a retrospective analysis in a cohort of patients who had an initial post-HCT decline in the absolute value of forced expiratory volume in 1 second (FEV1) of ≥10% or mid-expiratory flow rate of ≥25% but not meeting the criteria for BOS (pre-BOS). We examined the impact of clinical variables in patients with pre-BOS on the risk for subsequent BOS. Pre-BOS developed in 1325 of 3170 patients (42%), of whom 72 (5%) later developed BOS. Eighty-four patients developed BOS without detection of pre-BOS by routine screening. Among patients with pre-BOS, after adjusting for other significant variables, airflow obstruction (hazard ratio [HR], 2.0; 95% confidence interval [CI], 1.1 to 3.7; P = .02), percent-predicted FEV1 on decline (HR, .98; 95% CI, .97 to 1.0; P = .02), active cGVHD (HR, 7.7; 95% CI, 3.1 to 19.3; P \u3c .001), peripheral blood stem cell source (HR, 3.8; 95% CI, 1.7 to 8.6; P = .001), and myeloablative conditioning (HR, 2.0; 95% CI, 1.1 to 3.5; P = .02) were associated with subsequent BOS. The absence of airflow obstruction and cGVHD had a negative predictive value of 100% at 6 months for subsequent BOS, but the positive predictive value of both factors was low (cGVHD, 3%; any obstruction, 4%; combined, 6%). Several clinical factors at the time of pre-BOS, particularly active cGVHD and airflow obstruction, increase the risk for subsequent BOS. These factors merit consideration to be included in screening practices to improve the detection of BOS, with the caveat that the predictive utility of these factors is limited by the overall low incidence of BOS among patients with pre-BOS

Use of Sodium–glucose Cotransporter 2 Inhibitors in Patients with Chronic Kidney Disease

Chronic kidney disease (CKD) is a common complication in patients with diabetes mellitus. Recently, the class of sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) has been shown to have cardiovascular and renal benefits. The extent of the use of SGLT2-Is in patients with CKD is unknown. The objective of this study was to describe the prescription pattern of empagliflozin (the only available agent) in patients with CKD at Johns Hopkins Aramco Healthcare. This was a retrospective single-center analysis of patients with CKD over 2 years between January 1, 2020, and December 31, 2021. The prescription pattern of empagliflozin for adults (≥18 years) with CKD was determined quarterly. Among 2528 patients with CKD, 119 (5%) patients were prescribed empagliflozin during the first quarter of 2020. The number of patients steadily increased and reached 16% by the end of the study period. Despite the overwhelming evidence of their benefits, the overall utilization of SGLT2-Is was poor. Physicians' education is paramount to increase awareness about the benefits of SGLT2-Is as renoprotective and lifesaving medications

Prevalence of Microalbuminuria in Adult Patients with Sickle Cell Disease in Eastern Saudi Arabia

Background. Proteinuria is a common feature of sickle cell nephropathy (SCN) that can progress to renal insufficiency and end stage renal disease. Microalbuminuria (MA) is the earliest manifestation of SCN and precedes the development of overt proteinuria. In addition to the renal consequences, MA is linked to cardiovascular complications. Periodic screening and early detection of MA allow early intervention that may reduce the risk of progression to advanced renal failure and cardiovascular diseases. Objective. The aim of this study was to investigate the prevalence of MA in patients with SCD in the eastern region of Saudi Arabia. Methods. A prospective cross-sectional observational study was conducted at Johns Hopkins Aramco Healthcare (JHAH). Urine samples of SCD patients 18 years old and older were tested for the presence of MA using urinary albumin over creatinine ratio (ACR). Correlation was tested with multiple variables including age, gender, body mass index (BMI), hemoglobin level, blood pressure, blood transfusion history, pain episodes, and use of hydroxyurea. Results. Urine samples were tested on 72 patients. The mean age of the study cohort was 35±16.9 years. Microalbuminuria was detected in 18 patients (25%). No correlation was found with any of the tested variables. Conclusion. Microalbuminuria is a common finding in patients with SCD in eastern Saudi Arabia. Patients with SCD should be screened for MA, and those with positive tests should probably be treated with antiproteinuric agents that may slow the progression to advanced stages of renal failure and decrease the risk of cardiovascular diseases

Fusarium Infection in a Kidney Transplant Recipient Successfully Treated with Voriconazole

Fusarium infections in solid-organ transplant recipients are rare and carry high mortality. We report a case of a kidney transplant recipient who developed infection with Fusarium species. The patient received treatment with oral voriconazole for five months with good response

End-stage renal disease in patients with sickle cell disease

Sickle cell nephropathy is a severe complication of sickle cell disease (SCD) that has a wide range of manifestations, from asymptomatic microalbuminuria to end-stage renal disease (ESRD). The data on patients with SCD who develop ESRD are scarce. The aim of this study was to explore the course of patients with SCD who developed ESRD and received renal replacement therapy (RRT). The course of patients with SCD who developed ESRD and started dialysis at two centers in the Eastern Province of Saudi Arabia was retrospectively analyzed. Parameters included age at initiation of dialysis, survival until death or kidney transplantation, hospitalization due to pain crisis, disease-related parameters, and requirement for blood transfusion. Sixteen patients with SCD developed ESRD and started RRT with either hemodialysis or peritoneal dialysis. The mean age at initiation of dialysis was 46.6 years. The majority of patients (10 out of 16) were resistant to erythropoiesis-stimulating agents (ESA) and required blood transfusion repeatedly. Pain crises were infrequently encountered. Median survival was 54 months. Four patients received kidney transplantation with good outcome. In conclusion, most patients with SCD who developed ESRD were resistant to ESA and required repeated blood transfusion. The rate of hospitalization due to pain crisis was relatively low. Survival on dialysis was comparable to that of patients with no SCD, and the post-transplant course was relatively benign

Arachidonic acid protects against hypoxic injury in rat proximal tubules

Arachidonic acid protects against hypoxic injury in rat proximal tubules. Free fatty acids (FFA) and lysophospholipids accumulate during hypoxia (H) in rat proximal tubular epithelial cells partly as a result of increased phospholipase A2 (PLA2) activity. The role of FFA in mediating hypoxic injury and modulating PLA2 activity is not clear. In the present study, the effect of several FFA including arachidonic acid (AA, 20:4) on hypoxia-induced injury and PLA2 activity was assessed in freshly isolated rat proximal tubules. Hypoxia (H) was induced in the presence of either an unsaturated free fatty acid (uFFA) [AA or linoleic acid (LA, 18:2)] or a saturated FFA (sFFA) [palmitic (PA, 16:0) or myristic acid (MA, 14:0)]. Cell membrane injury was assessed by measuring lactate dehydrogenase release (LDH). AA markedly reduced LDH release during hypoxia in a dose dependent manner, while sFFA had no protective effect. LA showed similar protection to that observed with AA. AA did not affect buffer calcium concentration, buffer pH, intracellular pH or intracellular calcium concentration. Neither inhibiting the cyclooxygenase pathway with indomethacin, nor the lipoxygenase pathway with nordihydroguaiaretic acid (NDGA) had any effect on the AA observed cytoprotection. In vitro PLA2 activity in the control tubular extracts was compared to that following addition of AA or PA. PLA2 activity decreased significantly with AA but not with PA in a dose dependent manner. These data suggest that: (1) AA protects against hypoxic injury in rat proximal tubules. (2) This cytoprotection is not specific for AA and other uFFA have a similar effect. (3) AA significantly inhibits PLA2 activity. (4) AA induced cytoprotection may be related to a negative feedback inhibition of PLA2 activity

Angiosarcoma at the site of nonfunctioning arteriovenous fistula in a kidney transplant recipient

Angiosarcoma is a rare malignant neoplasm of the endothelial cells of blood vessels or lymphatics. We report a case of a 46-year-old male patient with a kidney transplant who developed epithelioid angiosarcoma at the site of a nonfunctioning arteriovenous fistula in the antecubital fossa 3 years after renal transplantation. The patient had skin, soft tissue, and bone metastasis on presentation. He died of systemic metastasis with respiratory failure

Nitric oxide kinetics during hypoxia in proximal tubules: Effects of acidosis and glycine

Nitric oxide kinetics during hypoxia in proximal tubules: effects of glycine and acidosis. In the present study, we directly monitored nitric oxide (NO) with an amperometric NO-sensor in suspensions of rat proximal tubules. Hypoxia-stimulated NO generation was characterized by an initial rise and a subsequent sustained increase which preceded cell membrane damage as assessed by lactic dehydrogenase (LDH) release. In contrast, the NO concentration remained unmeasurable in normoxic controls. Nitro-L-arginine-methyl ester (L-NAME) prevented the hypoxia-induced increase in NO in a dose dependent manner in parallel with incremental cytoprotection. The hypoxia-induced elevation in NO and the associated membrane injury were both markedly prevented by extracellular acidosis (pH 6.95). In vitro proximal tubular nitric oxide synthase (NOS) activity (3H-arginine to 3H-citrulline assay) was pH dependent with optimum activity at pH 8.0 and greatly reduced activity at acidic pH even in the presence of calcium and co-factors. However, glycine, a well recognized cytoprotective agent, did not attenuate the NO concentration during hypoxia. The present study therefore provides direct evidence that NO is generated by rat proximal tubules during hypoxia and demonstrates that the protective effect of low pH against hypoxic rat tubular injury is associated with an inhibition of this NO production