An Unusual Presentation of Pyelonephritis: Is It COVID-19 Related?

In severe cases of COVID-19, late complications such as coagulopathy and organ injury are increasingly described. In milder cases of the disease, the exact time frame and causal path of late-onset complications have not yet been determined. Although direct and indirect renal injury by SARS-CoV-2 has been confirmed, hemorrhagic renal infection or coagulative problems in the urinary tract have not yet been described. This case report describes a 35-year-old female without relevant medical history who, five days after having recovered from infection with SARS-CoV-2, had an unusual course of acute pyelonephritis of the right kidney and persistent fever under targeted antibiotic treatment. A hemorrhagic ureteral obstruction and severe swollen renal parenchyma preceded the onset of fever and was related to the developing pyelonephritis. Sudden thrombotic venous occlusion in the right eye appeared during admission. Symmetrical paresthesia in the limbs in combination with severe lower back pain and gastro-intestinal complaints also occurred and remained unexplained despite thorough investigation. We present the unusual combination of culture-confirmed bacterial hemorrhagic pyelonephritis with a blood clot in the proximal right ureter, complicated by retinal vein thrombosis, in a patient who had recovered from SARS-CoV-2-infection five days before presentation. The case is suspect of a COVID-19-related etiology.

Rational selection of a biomarker panel targeting unmet clinical needs in kidney injury.

The pipeline of biomarker translation from bench to bedside is challenging and limited biomarkers have been adopted to routine clinical care. Ideally, biomarker research and development should be driven by unmet clinical needs in health care. To guide researchers, clinical chemists and clinicians in their biomarker research, the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has developed a structured questionnaire in which the clinical gaps in current clinical pathways are identified and desirable performance specifications are predefined. In kidney injury, the high prevalence of the syndrome acute kidney injury (AKI) in the hospital setting has a significant impact on morbidity, patient survival and health care costs, but the use of biomarkers indicating early kidney injury in daily patient care remains limited. Routinely, medical labs measure serum creatinine, which is a functional biomarker, insensitive for detecting early kidney damage and cannot distinguish between renal and prerenal AKI. The perceived unmet clinical needs in kidney injury were identified through the EFLM questionnaire. Nephrologists within our tertiary care hospital emphasized that biomarkers are needed for (1) early diagnosis of in-hospital AKI after a medical insult and in critically ill patients, (2) risk stratification for kidney injury prior to a scheduled (elective) intervention, (3) kidney injury monitoring in patients scheduled to receive nephrotoxic medication and after kidney transplantation and (4) differentiation between prerenal AKI and structural kidney damage. The biomarker search and selection strategy resulted in a rational selection of an eleven-protein urinary panel for kidney injury that target these clinical needs. To assess the clinical utility of the proposed biomarker panel in kidney injury, a multiplexed LC-MS test is now in development for the intended translational research.

Urinary metabolites predict prolonged duration of delayed graft function in DCD kidney transplant recipients.

Extending kidney donor criteria, including donation after circulatory death (DCD), has resulted in increased rates of delayed graft function (DGF) and primary nonfunction. Here, we used Nuclear Magnetic Resonance (NMR) spectroscopy to analyze the urinary metabolome of DCD transplant recipients at multiple time points (days 10, 42, 180, and 360 after transplantation). The aim was to identify markers that predict prolonged duration of functional DGF (fDGF). Forty-seven metabolites were quantified and their levels were evaluated in relation to fDGF. Samples obtained at day 10 had a different profile than samples obtained at the other time points. Furthermore, at day 10 there was a statistically significant increase in eight metabolites and a decrease in six metabolites in the group with fDGF (N = 53) vis-à-vis the group without fDGF (N = 22). In those with prolonged fDGF (≥21 days) (N = 17) urine lactate was significantly higher and pyroglutamate lower than in those with limited fDGF (<21 days) (N = 36). In order to further distinguish prolonged fDGF from limited fDGF, the ratios of all metabolites were analyzed. In a logistic regression analysis, the sum of branched-chain amino acids (BCAAs) over pyroglutamate and lactate over fumarate, predicted prolonged fDGF with an AUC of 0.85. In conclusion, kidney transplant recipients with fDGF can be identified based on their altered urinary metabolome. Furthermore, two ratios of urinary metabolites, lactate/fumarate and BCAAs/pyroglutamate, adequately predict prolonged duration of fDGF.

Clinical predictors of escalating care in hepatic and renal cyst infection in autosomal dominant polycystic kidney and liver disease.

BACKGROUND: Cyst infection may occur in autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD). Antimicrobial agents often fail to control infection, leading to invasive action. We aimed to identify factors predicting escalation of care. METHODS: ADPKD and ADPLD patients were identified from local/national databases (2001-2013). Records were screened for patients meeting criteria for cyst infection (positive cyst aspirate and/or clinical findings). Factors that predict escalated care were identified with multivariate modified Poisson regression. RESULTS: We screened 1773 patients. A total of 77 patients with cyst infection (4.3%) were included for analysis (hepatic 36%; male 49%; age 54 ±; 13 years; ADPKD 95%; dialysis 9%, diabetes 18%, renal transplant 56%, eGFR [IQR 24-78] ml/min/1.73 m2 (excluding patients with a history of renal transplant or receiving dialysis)). A pathogen was identified in 71% of cases. Escherichia coli was the most common pathogen and accounted for 69% of cases. Initial treatment was limited to antibiotics in 87% of patients (n = 67), 40% included a fluoroquinolone. Ultimately, 48% of patients underwent some form of invasive action (escalation of care). Increasing white blood cell count (WBC) (RR 1.04 95%-CI 1.01-1.07, p = 0.008) was associated with escalating care, whereas an increase in time between transplant and infection (RR 0.92 95% CI 0.86-0.97, p = 0.005) and E. coli isolation (RR 0.55 95% CI 0.34-0.89, p = 0.02) were protective. CONCLUSION: High serum WBC, isolation of atypical pathogens and early infection after transplantation are factors that increase the risk of escalation of care in hepatic and renal cyst infection patients.

Household transmission of haemolytic uraemic syndrome associated with Escherichia coli O104:H4 in the Netherlands, May 2011.

Following the outbreak of haemolytic uraemic syndrome (HUS) and haemorrhagic colitis in Germany, two patients returning from a stay in Germany developed HUS due to Escherichia coli O104:H4 in the Netherlands. The index case developed symptoms eight days, and her child 15 days after their return. It is very likely that transmission resulted from secondary spread from mother to child. Recommendations should be made to prevent secondary transmission within households.

Analysis of efficacy of CVD 103-HgR live oral cholera vaccine against all-cause travellers' diarrhoea in a randomised, double-blind, placebo-controlled study.

Enterotoxigenic Escherichia coli (ETEC), which produces heat labile toxin (LT) and/or heat stable toxin (ST), is considered to be the most common known cause of travellers' diarrhoea (TD). Owing to the antigenic similarity between cholera toxin and LT, immunization with inactivated oral B-subunit/whole-cell cholera vaccine (BS-WC) offers short term (3 months) but significant (>67%) protection against TD caused by LT-related ETEC. Since it expresses the cholera toxin B (CTB) subunit, the live attenuated oral cholera vaccine strain CVD 103-HgR, may induce similar protection. A trial was performed to determine if CVD 103-HgR live oral cholera vaccine would provide a protective efficacy of at least 50% against TD. In addition, the protective efficacy of the vaccine against TD specifically due to LT-ETEC and LT/ST-ETEC was determined. Volunteers (n=134) travelling to Indonesia, India, Thailand or West-Africa were randomised to receive either a placebo (n=65) or the vaccine (n=69). In the placebo group, 46% reported an episode of diarrhoea, compared to 52% in the vaccine group. No significant group differences were found with regard to incidence, duration or severity of all caused TD or ETEC-associated TD. However, ETEC-associated TD occurred earlier in the placebo group (median 5 days), compared to the vaccine group (median 15 days). In conclusion, CVD 103-HgR live oral cholera vaccine failed to provide a 50% protection against TD. This study does not exclude that the vaccine may offer a short-lived protection against ETEC-associated TD. However, the power of the study was limited by the unexpected low incidence of LT-ETEC-associated diarrhoea (9% of all TD) compared to ST-associated TD (24% of all TD).