Incidence of Acute Kidney Injury and Associated Mortality among Individuals with Drug-Susceptible Tuberculosis in Uganda.

BACKGROUND: Although tuberculosis (TB) is associated with significant mortality and morbidity, its impact on kidney function is not well understood and is often attributed to anti-TB drugs. We aimed to assess the incidence of acute kidney injury (AKI) in the immediate post-TB diagnosis period in Uganda, a TB/HIV-endemic country in sub-Saharan Africa. METHODS: We included patients enrolled in an observational cohort study of adults diagnosed with drug-susceptible TB followed longitudinally. Adults (≥ 18years) without known kidney disease were enrolled between 8/2022-7/2023 at three regional hospitals serving 12.5% of the Ugandan population. Our primary outcome was incidence of KDIGO-defined AKI within two weeks of TB diagnosis. Other outcomes included predictors of AKI and its association with 30-day survival. RESULTS: A total of 156 adults were included. The median (IQR) age was 39 (28-53) years, most were male (68.6%) and 49.4% had HIV. People with HIV had shorter time to TB diagnosis from symptom onset (21[7-30] days) compared to HIV-negative participants (60[23-90] days), p<0.001. The incidence of AKI was 33.3% (52/156), and was similar between people with and without HIV. Proteinuria or hematuria at enrollment was associated with higher odds of AKI (OR-2.68, 95%CI 1.09-6.70, p∼0.033). AKI was associated with significant risk of mortality (aHR-8.22, 95% CI, 1.94-34.72, p ∼0.004) independent of HIV status. CONCLUSION: The overall incidence of AKI in the immediate post-TB diagnosis period is high and associated with increased mortality risk. Our findings suggest monitoring kidney function should be routine for patients with TB, including prior to treatment initiation.

The Future of Kidney Care in Low- and Middle-Income Countries: Challenges, Triumphs, and Opportunities.

CKD affects about 850 million people worldwide and is projected to be the fifth leading cause of death by 2040. Individuals from low- and middle-income countries (LMICs) bear the bulk of CKD. They face challenges including lack of awareness among the general population, as well as health care providers, unique risk factors such as genetic predispositions, infectious diseases, and environmental toxins, limited availability and affordability of diagnostic tests and medications, and limited access to KRTs. The inadequate health system infrastructure, human resources, and financing mechanisms to support comprehensive and integrated kidney care worsen the situation. Overcoming these challenges needs concerted efforts toward early detection, intervention, and multidisciplinary follow-up, policy, collaboration, advocacy, and financing. To achieve this, there is need for individual governments to include kidney health among the key health priorities and build capacity toward resilient health care systems. Integrating kidney care using the roadmaps of well-established management systems for other chronic diseases, such as HIV, has the potential to expedite the widespread adoption of kidney health. The aim of this article is to provide an overview of the current state and future prospects of kidney care in LMICs, highlighting the main challenges, ongoing efforts, and opportunities for improvement. We present case studies of exemplary efforts from three continents of the world with the highest densities of LMICs and propose potential strategies for a sustainable solution.

COVID-19-Associated Acute Kidney Injury and Longitudinal Kidney Outcomes.

Importance: COVID-19 infection is associated with a high incidence of acute kidney injury (AKI). Although rapid kidney function decline has been reported in the first few months after COVID-19-associated AKI (COVID-AKI), the longer-term association of COVID-AKI with kidney function remains unknown. Objective: To assess long-term kidney outcomes of patients who had COVID-19-associated AKI. Design, Setting, and Participants: This was a retrospective longitudinal multicenter cohort study conducted in a large hospital system using electronic health records data on adult hospitalized patients with AKI and COVID-19 or other illnesses. Included patients were hospitalized during the COVID-19 pandemic (March 2020-June 2022), were screened for SARS-CoV-2, had AKI, and survived to discharge, or had been hospitalized during the 5 years before the pandemic (October 2016-January 2020), had a positive influenza A or B test result, had AKI, and survived to discharge. Patients were followed up for a maximum of 2 years after hospital discharge. Data analyses were performed from December 2022 to November 2023. Exposure: COVID-19 and influenza. Main Outcomes and Measures: The primary outcome was major adverse kidney events (MAKE), defined as a composite of mortality and worsened kidney function (estimated glomerular filtration rate [eGFR] decline by ≥25% from discharge eGFR or kidney failure requiring dialysis). Multivariable time-to-event analyses were performed to compare MAKE between individuals with COVID-AKI and those who had AKI associated with other illnesses hospitalized during the same period. For further comparison, this outcome was assessed for a historic cohort of patients with influenza-associated AKI. Results: The study cohort included 9624 hospitalized patients (mean [SD] age, 69.0 [15.7] years; 4955 [51.5%] females) with AKI, including 987 patients with COVID-AKI, 276 with influenza-associated AKI, and 8361 with AKI associated with other illnesses (other-AKI). Compared with the other 2 groups, patients with COVID-19-associated AKI were slightly younger in age, had a higher baseline eGFR, worse baseline comorbidity scores, higher markers of illness severity, and longer hospital stay. Compared with the other-AKI group, the COVID-AKI group had lower MAKE (adjusted hazard ratio [aHR], 0.67; 95% CI, 0.59-0.75) due to lower all-cause mortality (aHR, 0.31; 95% CI, 0.24-0.39) and lower rates of worsened kidney function (aHR, 0.78; 95% CI, 0.69-0.88). Conclusions and Relevance: The findings of this multicenter cohort study indicate that survivors of hospitalization with COVID-AKI experience lower rates of MAKE, long-term kidney function decline, and mortality compared with patients with AKI associated with other illnesses.

The VUS Challenge in Cystic Kidney Disease: A Case-Based Review.

Genetic testing in nephrology is becoming increasingly important to diagnose patients and to provide appropriate care. This is especially true for autosomal dominant polycystic kidney disease (ADPKD) because this is a common cause of kidney failure and genetically complex. In addition to the major genes, PKD1 and PKD2 , there are at least six minor loci, and phenotypic, and in some cases, genetic overlap with other cystic disorders. Targeted next-generation sequencing, a low-cost, high-throughput technique, has made routine genetic testing viable in nephrology clinics. Appropriate pre- and post-testing genetic counseling is essential to the testing process. Carefully assessing variants is also critical, with the genetic report classifying variants in accordance with American College of Medical Genetics and Genomics guidelines. However, variant of uncertain significance (VUSs) may pose a significant challenge for the ordering clinician. In ADPKD, and particularly within PKD1 , there is high allelic heterogeneity; no single variant is present in more than 2% of families. The Mayo/Polycystic Kidney Disease Foundation variant database, a research tool, is the best current database of PKD1 and PKD2 variants containing over 2300 variants identified in individuals with polycystic kidney disease, but novel variants are often identified. In patients with a high pretest probability of ADPKD on the basis of clinical criteria, but no finding of a pathogenic (P) or likely pathogenic (LP) variant in a cystic kidney gene, additional evaluation of cystic gene VUS can be helpful. In this case-based review, we propose an algorithm for the assessment of such variants in a clinical setting and show how some can be reassigned to a diagnostic grouping. When assessing the relevance of a VUS, we consider both patient/family-specific and allele-related factors using population and variant databases and available prediction tools, as well as genetic expertise. This analysis plus further family studies can aid in making a genetic diagnosis.

Diagnosis of Chronic Kidney Disease and Assessing Glomerular Filtration Rate.

Chronic kidney disease (CKD) is a silent progressive disease. It is diagnosed by assessing filtration and markers of kidney damage such as albuminuria. The diagnosis of CKD should include not only assessing the glomerular filtration rate (GFR) and albuminuria but also the cause. The CKD care plan should include documentation of the trajectory and prognosis. The use of a combination of serum cystatin C and creatinine concentration offers a more accurate estimation of GFR. Social determinants of health are important to address as part of the diagnosis because they contribute to CKD disparities.

Chemotherapy-Associated Thrombotic Microangiopathy.

Thrombotic microangiopathy (TMA) is a syndrome of microangiopathic hemolytic anemia and thrombocytopenia with end-organ dysfunction. Although the advent of plasma exchange, immunosuppression, and complement inhibition has improved morbidity and mortality for primary TMAs, the management of secondary TMAs, particularly drug-induced TMA, remains less clear. TMA related to cancer drugs disrupts the antineoplastic treatment course, increasing the risk of cancer progression. Chemotherapeutic agents such as mitomycin-C, gemcitabine, and platinum-based drugs as well as targeted therapies such as antiangiogenesis agents and proteasome inhibitors have been implicated in oncotherapy-associated TMA. Among TMA subtypes, drug-induced TMA is less well-understood. Treatment generally involves withdrawal of the offending agent and supportive care targeting blood pressure and proteinuria reduction. Immunosuppression and therapeutic plasma exchange have not shown clear benefit. The terminal complement inhibitor, eculizumab, has shown promising results in some cases of chemotherapy-associated TMA including in re-exposure. However, the data are limited, and unlike in primary atypical hemolytic uremic syndrome, the role of complement in the pathogenesis of drug-induced TMA is unclear. Larger multicenter studies and unified definitions are needed to elucidate the extent of the problem and potential treatment strategies.

A unique case of purple urine: A case report and literature review.

Pigmented urine in a hospitalized patient has a broad differential diagnosis including urinary tract infection or bacterial colonization, hemolysis, rhabdomyolysis, and drugs. We present a case of purple urine in a patient who received methylene blue and hydroxocobalamin for catecholamine-refractory vasodilatory shock. The patient's purple urinary discoloration is presumed to have resulted from a combination of the blue and red pigments of methylene blue and hydroxocobalamin, respectively. As these drugs are increasingly being used to treat vasoplegia in cardiopulmonary bypass, it is important for clinicians to be aware of this benign cause of urine discoloration.