Is the combination of linagliptin and allopurinol better prophylaxis against post-contrast acute kidney injury? A multicenter prospective randomized controlled study.

BACKGROUND: Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD. METHODS: Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2nd received allopurinol, the 3rd group received linagliptin, and the 4th received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients. RESULTS: 20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 (p < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis. CONCLUSION: Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT03470454.

Hyperkalemia in chronic peritoneal dialysis patients.

Background. Chronic peritoneal dialysis (PD) patients often develop hypokalemia but less commonly hyperkalemia.Methods. We explored incidence and mechanisms of hyperkalemia in 779 serum samples from 33 patients on PD for 1 - 59 months. Normal serum potassium concentration was defined as 3.5 - 5.1 meq/l.Results. Mean monthly serum potassium concentrations were normal (except for 1 month), but we observed hypokalemia (<3.5 meq/l) in 5% and hyperkalemia (>5.1 meq/l) in 14% of 779 serum samples. Incidence of hyperkalemia did not change over time on PD: Year 1 (15%), Year 2 (11%), Year 3 (19%), Years 4-5 (22%). Hyperkalemia was mostly modest but occasionally extreme [5.2-5.4 meq/l (55%), 5.5-5.7 meq/l (21%), 5.8-6.0 meq/l (10%), >6.0 meq/l (14%)]. Of 31 patients (2 excluded due to brief PD time), 39% displayed hyperkalemia only, 23% displayed hypokalemia only, and the remainder (38%) displayed both or neither. Comparing hypokalemia-only with hyperkalemia-only patients, we found no difference in potassium chloride therapy, medications interrupting the renin-angiotensin system, small-molecule transport status, and renal urea clearance. We compared biochemical parameters from the hypokalemic and hyperkalemic serum samples and observed lower bicarbonate concentrations, higher creatinine concentrations, and higher urea nitrogen concentrations in the hyperkalemic samples (p < 0.001 for each), without difference in glucose concentrations.Conclusion. We observed hyperkalemia 3 times as frequently as hypokalemia in our PD population. High-potassium diet, PD noncompliance, increased muscle mass, potassium shifts, and/or the daytime period without PD might contribute to hyperkalemia.

How We Got Where We Are in Blood Pressure Targets.

PURPOSE OF REVIEW: While we started clinical trials evaluating the benefit of lowering systolic BP's >160 mm Hg and diastolic BPs of <130 mm Hg, the latest guideline suggests a target of <130/80 mm Hg in those with hypertension. This article summarizes exactly how we got to where we are looking over the last half-century. RECENT FINDINGS: Our understanding of systolic and diastolic blood pressure targets to improve cardiovascular outcomes has changed substantially over the past 5 decades. Regarding diastolic blood pressure targets to improve cardiovascular outcomes, initially the VA1 in 1967 had set the goal to <115 mmHg. Over time, several studies including the VA2, Hypertension Optimal Treatment (HOT), and United Kingdom Prospective Diabetes Study Group 38 (UKPDS38) highlighted even greater cardiovascular benefit with lower diastolic targets <80 mmHg, especially in diabetic patients. Of equal importance, multiple studies have focused the attention to systolic blood pressure targets. Starting in 1948 with the Framingham study, passing through the Systolic Hypertension in the Elderly Program (SHEP), Syst-Eur and Syst-China trials, all have set the systolic blood pressure goal <150 mmHg. Most recently, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial showed an improved cardiovascular outcome with a systolic blood pressure target <140 mmHg in patients with type 2 diabetes, while the Systolic Blood Pressure Intervention Trial (SPRINT) in non-diabetic patients moved it closer to 120 mmHg. There is "no one size fits all" when it comes to blood pressure targets to improve cardiovascular outcomes. To progress our understanding of individual blood pressure goals, future studies might develop a more standardized approach to highlight characteristics such as design and end point definitions while allowing clinical practitioners greater latitude to adapt guideline recommendations to individual patient characteristics and clinical needs.

Retrospective analysis of nontraumatic subdural hematoma incidence and outcomes in Egyptian patients with end-stage renal disease on hemodialysis.

BACKGROUND: The incidence of subdural hematoma (SDH) in chronic maintenance hemodialysis (CMH) patients may change over time, along with the evolving characteristics of the underlying populations. METHODS: We conducted a retrospective, single-center study at Cairo University hospitals, assessing the incidence, associated risk factors, and outcomes of nontraumatic SDH in CMH patients between January 2006 and January 2019. RESULTS: Out of 1217 CMH patients, nontraumatic SDH was diagnosed in 41 (3.37%) during the study, increasing with the enrollees' age but stable over the observation period and translating into an annual incidence rate of 28 per 1000 patients per year. SDH patients were likely to use central venous catheters, reported pruritis and history of bone fractures, and had higher phosphorus, parathyroid hormone, and alkaline phosphatase values (p < 0.001); however, there was no association with atrial fibrillation or use of anticoagulants. In the SDH cohort (n = 41), six patients did not need surgical intervention and 13 patients died before becoming surgically fit for intervention; mortality correlated with ischemic heart disease (p = 0.033) and the presence of atrial fibrillation or chronic anticoagulation with warfarin (p < 0.0001 for both), among others. Twenty-two patients received surgical operations and of these 2 died postoperatively; overall patient mortality was 12/41 (29.27%) at 30 days and 15/41 (36.59%) at 1 year. CONCLUSION: Our study demonstrated a striking enrichment for underlying comorbidities in those patients developing SDH and a high risk of immediate mortality. The benefit of chronic anticoagulation therapy should be carefully weighed against the risk of CNS bleed in MHD patients.

Immunosuppression in kidney transplant recipients with COVID-19 infection - where do we stand and where are we heading?

The appropriate immunosuppressive regimen in kidney transplant recipients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2/COVID-19) infection remains unclear. The impact of direct virus injury complicated by dysregulated hyperimmune response with overwhelming release of various cytokines in COVID-19 infected subjects contributes to the complexity of management. The largest concern of the practicing clinicians at current time is how to tailor maintenance immune-modulating therapy during active viral infection and the efficacy of the soon-to-be upcoming immunization for COVID-19. This targeted review aims to cover most of the current evidence on the effect of key maintenance immunosuppressive agents in COVID-19 infection and proposes a line of management to specific scenarios on this very rapidly evolving subject.

Eosinophilia and risk of incident end stage kidney disease.

BACKGROUND: Eosinophils in kidney disease are poorly understood and are often incidental findings on kidney biopsy. Eosinophilia in blood and renal biopsy tissue is associated with a host of immune and non-immune kidney diseases. The significance of eosinophilia in renal diseases has not been well addressed. We evaluated the presence of peripheral eosinophilia (> 4% of blood leukocytes) with biopsy tissue eosinophilia and their association with end-stage-kidney-disease (ESKD). METHODS: A nested case-control (2:1) of patients who underwent kidney biopsies at Johns Hopkins Hospital and Medical University of South Carolina from 2004 to 2018 were included in the study. From the 616 eligible patients, 178 patients were identified through the registry of kidney biopsies as 18 years or older without missing biopsy reports or hematology results. Controls (n = 154) had no ESKD at the time of case (n = 24) designation and were assembled using incident density sampling and matched on age and sex. The association of peripheral eosinophilia (> 4% of peripheral blood leukocytes) with the risk of progression to ESKD was evaluated using conditional logistic model after adjusting for clinical demographics. RESULTS: Among 178 patients, 65 (37%) had peripheral eosinophilia and 113 (63%) had no eosinophilia. Compared to patients without eosinophilia, patients with peripheral eosinophilia were notably male and had a higher serum creatinine at the time of their biopsy. Peripheral eosinophilia was associated with higher risk of ESKD (OR 15.9 [1.9, 134.7]) adjusted for patient demographics including hypertension, proteinuria and eGFR at the time of kidney biopsy. Peripheral eosinophilia had a significant linear association with kidney tissue eosinophils, 22 (standard deviation [SD] 20) per high power field (hpf) in 4-10% peripheral eosinophilia, 19 (SD 18) per hpf in ≥10% eosinophilia and 3 (SD 7) per hpf in no eosinophilia (P <  0.001). CONCLUSIONS: Peripheral eosinophilia is an independent predictor of tissue eosinophilia and subsequent progression to ESKD. Peripheral eosinophilia may be an early biomarker for underlying inflammation and disease, but further studies to investigate this clinical association are warranted.

Renal allograft surveillance with allospecific T-cytotoxic memory cells.

BACKGROUND: Allo-antigen-specific T-cytotoxic memory cells (TcM) which express CD40 ligand (CD154) in overnight lymphocyte co-culture are strongly associated with acute cellular rejection (ACR) seen in "for cause" biopsies for renal allograft dysfunction. Specifically, when the likelihood of rejection is increased, donor-specific allospecific TcM exceed those induced by HLA-non-identical third-party cell by 1.15-fold or greater. METHODS: The performance of allospecific TcM was evaluated retrospectively in primary renal transplant recipients (RTR) at routine clinical visits, cross-sectionally at presentation for biopsies, and serially. Performance metrics were sensitivity, specificity, positive and negative predictive values (PPV and NPV). RESULTS: Twenty-two primary RTR, median age 45 years (range 19-72) were tested with allospecific CD154 + TcM. Samples were obtained at the mean ± SD time interval of 806 ± 239 days after kidney transplantation. Six of 22 patients experienced biopsy proven T- Cell Mediated Rejection (TCMR). A seventh showed antibody mediated rejection (ABMR). Of these seven patients six demonstrated increased likelihood of rejection with allospecific TcM (sensitivity 83%). Ten of these 15 patients with no rejection had a negative test (specificity 67%). False positive tests were seen in five patients. Six out of 11 patients with positive tests had ACR/ABMR with a PPV of 54%, while 10 out of 11 patients with negative tests were non-rejecters with a NPV of 91%. CONCLUSION: Allospecific T-cytotoxic memory cells distinguished primary RTR with quiescent allografts from those with dysfunction. With serial surveillance measures, this test system may facilitate decisions to manage immunosuppression in RTR.

Diffuse membranoproliferative glomerulonephritis with focal sclerosis and renal amyloidosis in an adult male with autosomal dominant dystrophic epidermolysis bullosa: a case report.

Previous reports of glomerular disease in adult patients with autosomal dominant dystrophic epidermolysis bullosa (EB) are limited and include post-infectious glomerulonephritis, IgA nephropathy, amyloidosis, and leukocytoclastic vasculitis. To our knowledge, membranoproliferative glomerulonephritis (MPGN) has not been described before. We report a case of a 39-year-old male with autosomal dominant dystrophic EB, presenting with bilateral leg swelling of one-week duration. There was no other significant past medical history. The physical examination was remarkable for scars and erosions over all body areas, with all extremities with blisters and ulcers covered, absent finger and toenails and bilateral lower extremity edema. Serum creatinine was 0.9 mg/dL, albumin 1.3 g/dL and urine protein excretion 3.7 g/24 h. Viral markers (hepatitis-B, C, and HIV), complement c3 and c4 levels and auto-immune antibody profile all remained negative or within normal limits. Renal ultrasound and echocardiogram were normal. Renal biopsy recovered 14 glomeruli, all with proliferation of mesangial and endothelial cells as well as an expansion of the mesangial matrix, focal segmental sclerosis and amorphous homogeneous deposits demonstrating apple-green birefringence under polarized light with Congo red stain. Our observation emphasizes the importance of recognizing MPGN and secondary amyloidosis in patients with EB, especially with the availability of newer treatment modalities.

Artificial intelligence and machine learning trends in kidney care.

BACKGROUND: The integration of artificial intelligence (AI) and machine learning (ML) in kidney care has seen a significant rise in recent years. This study specifically analyzed AI and ML research publications related to kidney care to identify leading authors, institutions, and countries in this area. It aimed to examine publication trends and patterns, and to explore the impact of collaborative efforts on citation metrics. METHODS: The study used the Science Citation Index Expanded (SCI-EXPANDED) of Clarivate Analytics Web of Science Core Collection to search for AI and machine learning publications related to nephrology from 1992 to 2021. The authors used quotation marks and Boolean operator "or" to search for keywords in the title, abstract, author keywords, and Keywords Plus. In addition, the 'front page' filter was applied. A total of 5425 documents were identified and analyzed. RESULTS: The results showed that articles represent 75% of the analyzed documents, with an average author to publications ratio of 7.4 and an average number of citations per publication in 2021 of 18. English articles had a higher citation rate than non-English articles. The USA dominated in all publication indicators, followed by China. Notably, the research also showed that collaborative efforts tend to result in higher citation rates. A significant portion of the publications were found in urology journals, emphasizing the broader scope of kidney care beyond traditional nephrology. CONCLUSIONS: The findings underscore the importance of AI and ML in enhancing kidney care, offering a roadmap for future research and implementation in this expanding field.

Pneumoperitoneum and Acute Kidney Injury-An Integrative Clinical Concept Review.

An increased intraabdominal pressure, particularly when occurring during periods of hemodynamic instability or fluid overload, is regarded as a major contributor to acute kidney injury (AKI) in intensive care units. During abdominal laparoscopic procedures, intraoperative insufflation pressures up to 15 mmHg are applied, to enable visualization and surgical manipulation but with the potential to compromise net renal perfusion. Despite the widely acknowledged renal arterial autoregulation, net arterial perfusion pressure is known to be narrow, and the effective renal medullary perfusion is disproportionately impacted by venous and lymphatic congestion. At present, the potential risk factors, mitigators and risk-stratification of AKI during surgical pneumoperitoneum formation received relatively limited attention among nephrologists and represent an opportunity to look beyond mere blood pressure and intake-output balances. Careful charting and reporting duration and extent of surgical pneumoperitoneum represents an opportunity for anesthesia teams to better communicate intraoperative factors affecting renal outcomes for the postoperative clinical teams. In this current article, the authors are integrating preclinical data and clinical experience to provide a better understanding to optimize renal perfusion during surgeries. Future studies should carefully consider intrabdominal insufflation pressure as a key variable when assessing outcomes and blood pressure goals in these settings.

New onset hypertension after transplantation.

It has been reported that up to 90% of organ transplant recipients have suboptimal blood pressure control. Uncontrolled hypertension is a well-known culprit of cardiovascular and overall morbidity and mortality. In addition, rigorous control of hypertension after organ transplantation is a crucial factor in prolonging graft survival. Nevertheless, hypertension after organ transplantation encompasses a broader range of causes than those identified in non-organ transplant patients. Hence, specific management awareness of those factors is mandated. An in-depth understanding of hypertension after organ transplantation remains a debatable issue that necessitates further clarification. This article provides a comprehensive review of the prevalence, risk factors, etiology, complications, prevention, and management of hypertension after organ transplantation.

Mortality rate of COVID-19 infection in end stage kidney disease patients on maintenance hemodialysis: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been the most talked-about disease of the past few years. Patients with significant comorbidities have been at particular risk of adverse outcomes. This study looked at the outcomes and risk factors for adverse outcomes among patients on chronic hemodialysis for end-stage renal disease, a group of patients known to be particularly susceptible to infectious complications. AIM: To assess outcomes and risk factors for adverse outcomes of COVID-19 infection among patients on chronic hemodialysis. METHODS: We searched PubMed/MEDLINE, EMBASE, Reference Citation Analysis (https://www.referencecitationanalysis.com/) and Web of Science databases for relevant terms and imported the results into the Covidence platform. From there, studies were assessed in two stages for relevance and quality, and data from studies that satisfied all the requirements were extracted into a spreadsheet. The data was then analyzed descriptively and statistically. RESULTS: Of the 920 studies identified through the initial database search, only 17 were included in the final analysis. The studies included in the analysis were mostly carried out during the first wave. We found that COVID-19 incidence among patients on hemodialysis was significant, over 10% in some studies. Those who developed COVID-19 infection were most likely going to be hospitalized, and over 1 in 5 died from the infection. Intensive care unit admission rate was lower than the infection lethality rate. Biochemical abnormalities and dyspnea were generally reported to be associated with adverse outcomes. CONCLUSION: This systematic review confirms that patients on chronic hemodialysis are very high-risk individuals for COVID-19 infections, and a significant proportion was infected during the first wave. Their prognosis is overall much worse than in the general population, and every effort needs to be made to decrease their exposure.

ABO incompatibility in renal transplantation.

ABO blood group incompatibility (ABO-I) was historically considered an absolute contraindication to kidney transplantation due to the significant risk of acute antibody-mediated rejection and early graft loss. Nevertheless, the urge to minimize the gap between the candidates' number on the waitlist for kidney transplants and the available kidney donors encourage investigation into finding ways to use organs from ABO-I kidney donors, especially in the era of using more potent immunosuppression therapies. This review aims to discuss a general overview of ABO-I kidney transplantation and the different protocols adopted by some transplant centers to meaningfully overcome this barrier.

Hypertension and obesity in living kidney donors.

Over the past few decades, the shortage in the kidney donor pool as compared to the increasing number of candidates on the kidney transplant waitlist led to loosening of kidney donors' acceptance criteria. Hypertension and obesity represent risk factors for chronic kidney disease, both in native kidneys and those in kidney transplant recipients. While great progress has been made in kidney transplantation from living donors to benefit the recipient survival and quality of life, progress has been slow to fully risk-characterize the donors. This review critically reassesses the current state of understanding regarding the risk of end-stage kidney disease in those donors with obesity, hypertension or both. Accurate risk assessment tools need to be developed urgently to fully understand the risk glomerular filtration rate compensation failure in the remaining kidney of the donors.

Liver Kidney Crosstalk: Hepatorenal Syndrome.

The dying liver causes the suffocation of the kidneys, which is a simplified way of describing the pathophysiology of hepatorenal syndrome (HRS). HRS is characterized by reversible functional renal impairment due to reduced blood supply and glomerular filtration rate, secondary to increased vasodilators. Over the years, HRS has gained much attention and focus among hepatologists and nephrologists. HRS is a diagnosis of exclusion, and in some cases, it carries a poor prognosis. Different classifications have emerged to better understand, diagnose, and promptly treat this condition. This targeted review aims to provide substantial insight into the epidemiology, pathophysiology, diagnosis, and management of HRS, shed light on the various milestones of this condition, and add to our current understanding.

Coronavirus disease 2019 and renal transplantation.

Ever since the severe acute respiratory syndrome virus causing coronavirus disease 2019 (COVID-19) struck the world, global health strategies have changed significantly. According to the Centers for Disease Control and Prevention, kidney transplant recipients are stratified as being high risk of developing fatal illness from COVID-19 infection. Kidney transplant is the gold-standard treatment for end-stage kidney disease subjects. During the pandemic, significant concerns have emerged regarding continuation of kidney transplant surgeries and management of kidney transplant recipients post-transplant. The added risk of immunosuppression in this cohort was and remains a theoretical concern, posing a potential risk of transplantation rather than benefit. This comprehensive review aims to cover most of the faced challenges in kidney transplantation in different stages of the pandemic. In addition, it will elucidate the epidemiology, nature, course of the disease, surgical consideration in donors and recipients as well as role of immunosuppression and management of COVID-19 infected kidney transplant recipients during these extraordinary circumstances.

Liver transplantation during global COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory disease respiratory syndrome coronavirus-2 has significantly impacted the health care systems globally. Liver transplantation (LT) has faced an unequivocal challenge during this unprecedented time. This targeted review aims to cover most of the clinical issues, challenges and concerns about LT during the COVID-19 pandemic and discuss the most updated literature on this rapidly emerging subject.

Systematic Review and Meta-Analysis of Antibiotic and Antimicrobial Lock Solutions for Prevention of Hemodialysis Catheter-Related Infections.

Catheter-related bloodstream infection (CRBSI) with hemodialysis catheters are associated with increased mortality, morbidity and pose significant financial burden on healthcare. Antibiotic and antimicrobial locking solutions are effective in reducing risk of CRBSI. From inception to April 2020, we looked for relevant clinical controlled trials throughout the following databases: EBSCO, PubMed, Cochrane CENTRAL, MEDLINE, EMBASE, clinicaltrial.gov, and Google Scholar performing a metanalysis comparing antibiotic and antimicrobial lock solutions to heparin. Twenty-six studies with 4,967 patients reported the incidence of catheter-related bacteremia (CRB). The overall pooled risk ratio (RR) showed that the intervention group was associated with a significantly lower incidence of CRB by 30% compared with heparin (RR = 0.30, 95% confidence interval [CI] [0.25, 0.36], p < 0.001). Subgroup analysis showed that administration of antibiotic regimens led to a decreased risk of CRB episodes by 28% compared with the heparin group (RR = 0.28, 95% CI [0.21, 0.37], p < 0.0001). Antimicrobial solutions was associated with reduced risk of CRB by 32% compared with patients of the control group (RR = 0.32, 95% CI [0.25, 0.41], p < 0.0001). A test of subgroup differences was revealed no significant favoring of any of the two interventions. Both antibiotic and antimicrobial solutions are effective in reducing CRBSI.