Using herbs medically without knowing their composition: are we playing Russian roulette?

Herbal medicine, a form of complementary and alternative medicine (CAM), is used throughout the world, in both developing and developed countries. The ingredients in herbal medicines are not standardized by any regulatory agency. Variability exists in the ingredients as well as in their concentrations. Plant products may become contaminated with bacteria and fungi during storage. Therefore, harm can occur to the kidney, liver, and blood components after ingestion. We encourage scientific studies to identify the active ingredients in herbs and to standardize their concentrations in all herbal preparations. Rigorous studies need to be performed in order to understand the effect of herbal ingredients on different organ systems as well as these substances' interaction with other medications.

Radiomics-Based Image Phenotyping of Kidney Apparent Diffusion Coefficient Maps: Preliminary Feasibility & Efficacy.

Given the central role of interstitial fibrosis in disease progression in chronic kidney disease (CKD), a role for diffusion-weighted MRI has been pursued. We evaluated the feasibility and preliminary efficacy of using radiomic features to phenotype apparent diffusion coefficient (ADC) maps and hence to the clinical classification(s) of the participants. The study involved 40 individuals (10 healthy and 30 with CKD (eGFR < 60 mL/min/1.73 m2)). Machine learning methods, such as hierarchical clustering and logistic regression, were used. Clustering resulted in the identification of two clusters, one including all individuals with CKD (n = 17), while the second one included all the healthy volunteers (n = 10) and the remaining individuals with CKD (n = 13), resulting in 100% specificity. Logistic regression identified five radiomic features to classify participants as with CKD vs. healthy volunteers, with a sensitivity and specificity of 93% and 70%, respectively, and an AUC of 0.95. Similarly, four radiomic features were able to classify participants as rapid vs. non-rapid CKD progressors among the 30 individuals with CKD, with a sensitivity and specificity of 71% and 43%, respectively, and an AUC of 0.75. These promising preliminary data should support future studies with larger numbers of participants with varied disease severity and etiologies to improve performance.

In CKD, the effect of dapagliflozin on kidney outcomes did not vary by T2DM status or CKD cause.

SOURCE CITATION: Wheeler DC, Stefánsson BV, Jongs N, et al. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: a prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021;9:22-31. 33338413.

SGLT2 inhibitors reduce all-cause mortality.

SOURCE CITATION: Silverii GA, Monami M, Mannucci E. Sodium-glucose co-transporter-2 inhibitors and all-cause mortality: a meta-analysis of randomized controlled trials. Diabetes Obes Metab. 2021;23:1052-6. 33283969.

Novel Use of Premixed Dialysate Bags during Water Supply Interruption in Acute Hospital Setting.

Patients on dialysis are exposed to large amounts of water during conventional intermittent hemodialysis; hence, there are strict regulations regarding the quality of water used to prepare dialysate. Occasionally, water systems fail due to natural disasters or structural supply issues, such as water-main breaks or unplanned changes in municipal or facility water quality. It is critical to regularly monitor and immediately recognize such a failure and take steps to avoid exposing the patients to contaminants. In addition to the recognition of the problem, the ability to pivot and continue to provide safe treatment to inpatients who are dependent on dialysis is essential, both from an ultrafiltration and a clearance standpoint. At our hospital, an unforeseen water disruption occurred and we were able to continue to provide KRT with premade, bagged dialysate to mitigate the effect on our patients on dialysis. This is a novel method using available machines and dialysate, which we normally stock for continuous KRT, for short dialysis sessions. The methodology is similar to that which has been widely used for short daily home hemodialysis with low dialysate flow rate. Because this situation occurred in the midst of the SARS-CoV-2 pandemic, we had to be mindful of dialysate volumes and staffing time. Here, we present our investigation into the cause of the water-system failure and how we quickly implemented the alternative dialysis method. Short dialysis with low-flow dialysate will not deliver the same Kt/V per session as standard dialysis; however, this method was successfully implemented and tailored with adjustments for patients requiring higher clearance for specific indications, such as severe hyperkalemia.

In older adults with CKD and mild acidosis, oral sodium bicarbonate did not improve physical function.

SOURCE CITATION: Witham MD, Band M, Chong H, et al. Sodium bicarbonate to improve physical function in patients over 60 years with advanced chronic kidney disease: the BiCARB RCT. Health Technol Assess. 2020;24:1-90. 32568065.

Hemoperitoneum in a Peritoneal Dialysis Patient: Ruptured Ectopic Pregnancy.

Hemoperitoneum is a well-recognized complication in female peritoneal dialysis (PD) patients of childbearing age. Bloody effluent is commonly of minor nature, presenting during menstruation or midcycle, resolving after a few rapid exchanges without a need for further intervention. One must remain vigilant, however, and consider a broader differential diagnosis when hemoperitoneum is persistent or severe, as it indicates a serious and potentially life-threatening etiology. We report 2 episodes of hemoperitoneum in a PD patient occurring more than 1.5 years apart, with different underlying etiologies. The more dramatic second episode was due to a ruptured ectopic pregnancy, a condition which had not been reported as a cause of hemoperitoneum in dialysis patients to date and requires a high index of suspicion and prompt surgical intervention.

Three-Stream, Bicarbonate-Based Hemodialysis Solution Delivery System Revisited: With an Emphasis on Some Aspects of Acid-Base Principles.

Hemodialysis patients can acquire buffer base (i.e., bicarbonate and buffer base equivalents of certain organic anions) from the acid and base concentrates of a three-stream, dual-concentrate, bicarbonate-based, dialysis solution delivery machine. The differences between dialysis fluid concentrate systems containing acetic acid versus sodium diacetate in the amount of potential buffering power were reviewed. Any organic anion such as acetate, citrate, or lactate (unless when combined with hydrogen) delivered to the body has the potential of being converted to bicarbonate. The prescribing physician aware of the role that organic anions in the concentrates can play in providing buffering power to the final dialysis fluid, will have a better knowledge of the amount of bicarbonate and bicarbonate precursors delivered to the patient.

Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.

Patient-specific phosphorus mobilization clearance during nocturnal and short daily hemodialysis.

The kinetics of plasma phosphorus during different hemodialysis (HD) modalities are incompletely understood. We recently demonstrated that a pseudo one-compartment kinetic model including phosphorus mobilization from various body compartments into extracellular fluids can describe intradialytic and postdialytic rebound kinetics of plasma phosphorus during conventional and short 2-hour HD treatments. In this model, individual patient differences in phosphorus kinetics were characterized by a single parameter, the phosphorus mobilization clearance (K(M)). In this report we determined K(M) in patients treated by in-center nocturnal HD (ICNHD) and short daily HD (SDHD) with low dialyzer phosphate clearance. In the ICNHD study, eight patients underwent 8-hour HD treatments where intradialytic and postdialytic plasma samples were collected; K(M) values were determined by nonlinear regression of plasma concentration as a function of time. In the SDHD study, five patients were studied during 28 treatments for approximately 3 hours. Here, K(M) was calculated using only predialytic and postdialytic plasma phosphorus concentrations. Dialyzer phosphate clearances were 134 ± 20 (mean ± SD) and 95 ± 16 mL/min during ICNHD and SDHD, respectively. K(M) values for the respective therapies were 124 ± 83 and 103 ± 33 mL/min, comparable to those determined previously during conventional and short HD treatments of 98 ± 44 mL/min. When results from ICNHD, SDHD, and previous HD modalities were combined, K(M) was directly correlated with postdialytic body weight (r = 0.38, P = 0.025) and inversely correlated with predialytic phosphorus concentration (r = -0.47, P = 0.005). These findings suggest that phosphorus kinetics during various HD modalities can be described by a pseudo one-compartment model.

Genetic association and gene-gene interaction analyses in African American dialysis patients with nondiabetic nephropathy.

BACKGROUND: African Americans have increased susceptibility to nondiabetic nephropathy relative to European Americans. STUDY DESIGN: Follow-up of a pooled genome-wide association study (GWAS) in African American dialysis patients with nondiabetic nephropathy; novel gene-gene interaction analyses. SETTING & PARTICIPANTS: Wake Forest sample: 962 African American nondiabetic nephropathy cases, 931 non-nephropathy controls. Replication sample: 668 Family Investigation of Nephropathy and Diabetes (FIND) African American nondiabetic nephropathy cases, 804 non-nephropathy controls. PREDICTORS: Individual genotyping of top 1,420 pooled GWAS-associated single-nucleotide polymorphisms (SNPs) and 54 SNPs in 6 nephropathy susceptibility genes. OUTCOMES: APOL1 genetic association and additional candidate susceptibility loci interacting with or independently from APOL1. RESULTS: The strongest GWAS associations included 2 noncoding APOL1 SNPs, rs2239785 (OR, 0.33; dominant; P = 5.9 × 10(-24)) and rs136148 (OR, 0.54; additive; P = 1.1 × 10(-7)) with replication in FIND (P = 5.0 × 10(-21) and 1.9 × 10(-05), respectively). rs2239785 remained associated significantly after controlling for the APOL1 G1 and G2 coding variants. Additional top hits included a CFH SNP (OR from meta-analysis in the 3,367 African American cases and controls, 0.81; additive; P = 6.8 × 10(-4)). The 1,420 SNPs were tested for interaction with APOL1 G1 and G2 variants. Several interactive SNPs were detected; the most significant was rs16854341 in the podocin gene (NPHS2; P = 0.0001). LIMITATIONS: Nonpooled GWASs have not been performed in African American patients with nondiabetic nephropathy. CONCLUSIONS: This follow-up of a pooled GWAS provides additional and independent evidence that APOL1 variants contribute to nondiabetic nephropathy in African Americans and identified additional associated and interactive nondiabetic nephropathy susceptibility genes.

Fractional excretion of urea in pre-eclampsia: a clinical observation.

INTRODUCTION: Pre-eclampsia is one of the leading causes of maternal and fetal mortality and morbidity. It occurs in 7% of all the pregnancies and accounts for 80% of the cases of pregnancy-induced hypertension. Diagnosis of pre-eclampsia in patients with pre-existing chronic kidney disease, proteinuria, and hypertension is a dilemma. The fractional excretion of urea has been described as a marker for renal perfusion. Since pre-eclampsia is associated with a marked decline in renal perfusion, we explored the utility of the fractional excretion of urea as a marker for pre-eclampsia. MATERIALS AND METHODS: Urine and serum chemistries were evaluated in 6 pregnant women with pre-eclampsia on their first visit, immediately prior to delivery, and postpartum. For each of these three measurements, the fractional excretion of urea was calculated and proteinuria was assessed by random urine protein-creatinine ratio or 24-hour urine protein studies. RESULTS: In patients diagnosed with pre-eclampsia, the fractional excretion of urea decreased substantially from higher values obtained during the 3rd trimester to values consistent with renal hypoperfusion (< 35%) just prior to delivery, and it rapidly normalized immediately after delivery. CONCLUSIONS: Alterations in fractional excretion of urea, which suggest a decreased renal perfusion, may be a useful tool in supporting the diagnosis of preeclampsia.

Solute kinetics with short-daily home hemodialysis using slow dialysate flow rate.

"NxStage System One()" is increasingly used for daily home hemodialysis. The ultrapure dialysate volumes are typically between 15 L and 30 L per dialysis, substantially smaller than the volumes used in conventional dialysis. In this study, the impact of the use of low dialysate volumes on the removal rates of solutes of different molecular weights and volumes of distribution was evaluated. Serum measurements before and after dialysis and total dialysate collection were performed over 30 times in 5 functionally anephric patients undergoing short-daily home hemodialysis (6 d/wk) over the course of 8 to 16 months. Measured solutes included beta(2) microglobulin (beta(2)M), phosphorus, urea nitrogen, and potassium. The average spent dialysate volume (dialysate plus ultrafiltrate) was 25.4+/-4.7 L and the dialysis duration was 175+/-15 min. beta(2) microglobulin clearance of the polyethersulfone dialyzer averaged 53+/-14 mL/min. Total beta(2)M recovered in the dialysate was 106+/-42 mg per treatment (n=38). Predialysis serum beta(2)M levels remained stable over the observation period. Phosphorus removal averaged 694+/-343 mg per treatment with a mean predialysis serum phosphorus of 5.2+/-1.8 mg/dL (n=34). Standard Kt/V averaged 2.5+/-0.3 per week and correlated with the dialysate-based weekly Kt/V. Weekly beta(2)M, phosphorus, and urea nitrogen removal in patients dialyzing 6 d/wk with these relatively low dialysate volumes compared favorably with values published for thrice weekly conventional and with short-daily hemodialysis performed with machines using much higher dialysate flow rates. Results of the present study were achieved, however, with an average of 17.5 hours of dialysis per week.

MYH9 is associated with nondiabetic end-stage renal disease in African Americans.

As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39-0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.

Thrombotic thrombocytopenic purpura after cephalosporin administration: a possible relationship.

BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder. The pathogenesis is believed to be mediated by an autoantibody directed against the metalloproteinase responsible for the degradation of the very-high-molecular-weight multimers of the vWF. The syndrome can be precipitated by a variety of conditions, and certain medications also have been implicated. CASE REPORTS: The cases of two patients who took a cephalosporin antibiotic, cephalexin (Keflex, Eli Lilly), and then developed TTP are reported. One patient subsequently received a third-generation cephalosporin, ceftriaxone (Rocephin, Roche), without adverse reaction. Of interest, one patient had taken cefaclor (Ceclor, Eli Lilly) 8 years before and had also developed TTP at that time. The other patient also took cefaclor for approximately 3 weeks before taking cephalexin. In addition, she had had a dose of clarithromycin (Biaxin, Abbott Laboratories) the day before the onset of the TTP symptoms. CONCLUSIONS: To our knowledge, TTP has not been reported previously after administration of cephalosporin antibiotics. Attention is called to the possibility that this syndrome may occur after exposure to some of these drugs, although the incidence is very rare or, alternatively, underdiagnosed.