OBJECTIVES: To clarify the causal relationship between the level of cytoplasmic unactivated mineralocorticoid receptor (MR) and the development of tubulointerstitial nephritis (TIN), and to evaluate the impact of MR on dyslipidemia, particularly secondary hyperlipemia, in patients with diabetic kidney disease. METHODS: We conducted a two-sample Mendelian randomization study using genome-wide association study (GWAS) summary data. Genetic variants associated with MR levels were selected as exposures, with TIN and lipid profiles [including low-density lipoprotein cholesterol (LDL-C), triglyceride, and high-density lipoprotein cholesterol] as outcomes. A two-step Mendelian randomization approach was used to assess TIN as a mediator, employing inverse variance weighted regression as the primary analysis, supplemented by Mendelian randomization-Egger, weighted median, and sensitivity analyses. RESULTS: Cytoplasmic unactivated MR level exhibited a significant causal association with a decreased risk of TIN (OR = 0.8598, 95% CI [0.7775-0.9508], P < 0.001). Although no significant causal relationship was identified between MR level and secondary hyperlipemia, a potential association of cytoplasmic unactivated MR level with lower LDL-C levels was observed (OR = 0.9901, 95% CI [0.9821-0.9983], P = 0.018). Additionally, TIN exhibited causal links with secondary hyperlipemia (OR = 1.0016, 95% CI [1.0002-1.0029], P = 0.020) and elevated LDL-C (OR = 1.0111, 95% CI [1.0024-1.0199], P = 0.012), particularly LDL-C in European males (OR = 1.0230, 95% CI [1.0103-1.0358], P < 0.001). Inverse Mendelian randomization analysis revealed causal relationships between TIN and genetically predicted triglyceride (OR = 0.7027, 95% CI [0.6189-0.7978], P < 0.001), high-density lipoprotein cholesterol (OR = 1.1247, 95% CI [1.0019-1.2626], P = 0.046), and LDL-C (OR = 0.8423, 95% CI [0.7220-0.9827], P = 0.029). Notably, TIN mediated 16.7% of the causal association between MR and LDL-C levels. CONCLUSIONS MR plays a critical role in the development of TIN and lipid metabolism, highlighting the potential of MR-antagonists in reducing renal damage and lipid metabolism-associated complications.
Humans ; Mendelian Randomization Analysis ; Nephritis, Interstitial/metabolism* ; Receptors, Mineralocorticoid/genetics* ; Lipid Metabolism/genetics* ; Genome-Wide Association Study ; Male ; Female ; Polymorphism, Single Nucleotide ; Dyslipidemias/metabolism*

This study reports the diagnosis and treatment of a 26-year-old pregnant woman with severe malnutrition combined with acute pyelonephritis causing sepsis, refractory septic shock and multiple organ failure. A female patient, 26 years old, was admitted to hospital mainly due to "menelipsis for more than 19 weeks, nausea and vomiting for 20 days, fever with fatigue for 3 days". At the end of 19 weeks of intrauterine pregnancy, the patient presented with fever accompanied by urinary tract irritation. Laboratory tests showed elevated inflammatory indicators, and ultrasonography showed bilateral pelvicalyceal dilation. She was diagnosed with acute pyelonephritis, sepsis, acute kidney injury (AKI) and severe malnutrition. After a whole-hospital consultation, the patient was treated with meropenem and vancomycin as antimicrobial therapy, and bilateral nephrostomy drainage was performed simultaneously. After that, the patient suffered a sudden decrease in blood pressure, blood oxygen saturation, and rapid heart rate. Septic shock with multiple organ dysfunction was considered, and she was transferred to intensive care unit (ICU) immediately. After the patient was transferred to ICU, emergency tracheal intubation and ventilator-assisted ventilation were performed. Rapid fluid resuscitation was administered for the patient. While pulse indicator continuous cardiac output (PICCO) monitoring was performed, norepinephrine, terlipressin, and methylene blue were administered to maintain peripheral vascular resistance. Since the patient developed septic cardiomyopathy and cardiogenic shock later, levosimendan and epinephrine were admi-nistered to improve cardiac function. While etiological specimens were delivered, meropenem, teicoplanin and caspofungin were given as initial empiric antimicrobial therapy. Unfortunately, the intrauterine fetal death occurred on the night of admission to ICU. On the 3rd day of ICU admission, a still-born child was delivered vaginally with 1/5 defect of the fetal membrane. On the 6th day of ICU admission, the patient had fever again with elevated inflammatory indicators. After excluding infection in other parts, intrau-terine infection caused by incomplete delivery of fetal membrane was considered. Then emergency uterine curettage was performed and the infection gradually improved. Later the laboratory results showed that the nephrostomy drainage was cultured for Escherichia coli and uterine, cervical and vaginal secretions were cultured for Candida albicans. Due to severe infection and intrauterine incomplete abortion, the patient developed disseminated intravascular coagulation (DIC). Active antimicrobial therapy and blood product supplement were given. However, the patient was critically ill with significant decrease in hemoglobin and platelets combined with multiple organ failure. Thrombotic microangiopathy (TMA) was not excluded yet, so plasma exchange was performed for the patient in order not to delay treatment. The patient underwent bedside continuous renal replacement therapy (CRRT) for AKI. The patient was complicated with acute liver injury, and the liver function gradually returned to normal after liver protection, antimicrobial therapy and other treatments. Due to the application of large doses of vasoactive drugs, the extremities of the patient gradually developed cyanosis and ischemic necrosis. Local dry gangrene of the bilateral toes remained at the time of discharge. In general, the patient suffered from septic shock, cardiogenic shock, combined with DIC and multiple organ dysfunction. After infection source control, antimicrobial therapy, uterine curettage, blood purification treatment, nutritional and metabolic support, the patient was discharged with a better health condition.
Humans ; Female ; Pyelonephritis/complications* ; Pregnancy ; Adult ; Multiple Organ Failure/etiology* ; Shock, Septic/etiology* ; Sepsis/etiology* ; Pregnancy Complications ; Pregnancy Complications, Infectious ; Malnutrition/complications*

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare autosomal dominant hereditary disorder characterized by hyperuricemia, gout, impaired urinary concentration, and progressive renal failure. It is primarily caused by mutations in uromodulin (UMOD) gene. This study reports a family with ADTKD in which whole-exome sequencing and Sanger sequencing identified a missense mutation in the UMOD gene, c.761A>C (p.H254P), present in both the proband and affected relatives. According to American College of Medical Genetics and Genomics (ACMG) guidelines, this variant is classified as likely pathogenic. The mutation results in an amino acid substitution that may impair UMOD protein folding and intracellular trafficking. UMOD gene mutations are associated with ADTKD, and genetic testing plays a vital role in the early diagnosis and treatment of this condition, highlighting its importance in the diagnosis of rare kidney diseases.
Adult ; Humans ; Male ; Exome Sequencing ; Mutation ; Mutation, Missense ; Nephritis, Interstitial/genetics* ; Pedigree ; Uromodulin/genetics*

Objective: To examine the modalities of treatment and clinical outcomes of emphysematous pyelonephritis (EPN), in order to improve the survival rate of EPN patients. Methods: Totally 14 patients diagnosed as EPN between October 2011 and November 2020 at Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were included in this article. Data collection including patient demographics, clinical manifestations, management and clinical outcomes were conducted by retrospective charts review, after receiving the institutional review board's approval. There were 11 females and 3 males with a median age of 59 years (range: 52 to 73 years). The lesions were located on the left side in 10 patients and right side in 4 patients. All the 14 patients suffered from fever, and present with severe sepsis or septic shock. The median time from symptom onset to admission to hospital was 3 days(range: 2 to 5 days). All cases had diabetes mellitus. Escherichia coli was the most common organism been cultured (11 cases), while Klebsiella pneumonia was the second (3 cases). CT scan showed bubbly or located gas in the renal parenchyma in 5 cases and presence of steaky or mottled gas in the renal parenchyma in 9 cases. All patients had been admitted to ICU for anti-septic shock therapy. Three patients had undergone percutaneous catheter drainage along with broad-spectrum antibiotics therapy while 3 patients had immediate nephrectomy, the other 8 cases had a combination of an initial percutaneous catheter drainage and second stage nephrectomy. Results: In this case series, 3 patients were died from EPN while the other 11 were survived. The median ICU stay time was 6 days (range: 3 to 11 days). Of the 3 patients died from EPN, 2 had undergone percutaneous catheter drainage along and 1 had received immediate nephrectomy. Among the 11 patients who were survived, only 1 had received percutaneous catheter drainage while the other 10 received nephrectomy (8 patients had staged nephrectomy). Follow-up was performed 6 months after discharge. Of the 11 surviving patients, 2 were lost to follow-up, and the remaining 9 patients had an creatine level of (118.4±29.4) μmol/L (range: 89 to 176 μmol/L). Conclusions: For patients coupled with diabetes who were initially diagnosed as acute pyelonephritis, the possibility of EPN should be considered when the disease progressed rapidly especially septic shock occurred. On the basis of empirical broad-spectrum antibiotics therapy and standardized anti-septic shock treatment, a combination of an initial percutaneous catheter drainage and second stage nephrectomy could be efficacious.
Aged ; Emphysema/therapy* ; Escherichia coli Infections ; Female ; Humans ; Male ; Middle Aged ; Pyelonephritis/therapy* ; Retrospective Studies ; Treatment Outcome

Acute Disease ; Allografts ; Humans ; Kidney ; Kidney Transplantation ; Nephritis ; Pyelonephritis ; Transplantation, Homologous

OBJECTIVES: Tubulointerstitial diseases is one of the common causes of renal dysfunction. Some rare pathological types are easy to be misdiagnosed and missedly diagnosed because of their low prevalence and relatively insufficient understanding, which affects the treatment and prognosis of patients. This study aims to explore clinical manifestations and pathological characteristics of several rare tubulointerstitial diseases, and therefore to improve their diagnosis and treatment. METHODS: A total of 9 363 patients diagnosed by renal biopsy in the Department of Nephrology, Second Xiangya Hospital, Central South University from November 2011 to September 2021 were selected. Six cases of light chain cast nephropathy (LCCN), 2 cases of light chain proximal tubulopathy (LCPT), 1 case of LCCN with LCPT, 4 cases of genetic tubulointerstitial disease, and 6 cases of non-genetic related tubulointerstitial lesion were screened out, and their clinical manifestations and renal biopsy pathological results were collected, compared, and analyzed. RESULTS: Patients with LCCN presented with mild to moderate anemia, microscopic hematuria, and mild to moderate proteinuria. Compared with patients with LCPT, proteinuria and anemia were more prominent in patients with LCCN. Five patients with LCCN and 2 patients with LCPT had elevated serum free kappa light chain. Five patients with LCCN presented clinically with acute kidney injury (AKI). Two patients with LCPT and 1 patient with LCCN and LCPT showed CKD combined with AKI, and 1 LCPT patient presented with typical Fanconi syndrome (FS). Five patients with LCCN, 2 patients with LCPT, and 1 patient with LCCN and LCPT were diagnosed with multiple myeloma. Five patients with LCCN had kappa light chain restriction in tubules on immunofluorescence and a "fractured" protein casts with pale periodic acid-Schiff (PAS) staining on light microscopy. Immunohistochemical staining of 2 LCPT patients showed strongly positive kappa light chain staining in the proximal tubular epithelial cells. And monoclonal light chain crystals in crystalline LCPT and abnormal lysosomes and different morphological inclusion bodies in noncrystalline LCPT were observed under the electron microscope. Six patients with LCCN were mainly treated by chemotherapy. Renal function was deteriorated in 1 patient, was stable in 4 patients, and was improved in 1 patient. Two patients with LCPT improved their renal function after chemotherapy. Four patients with genetic tubulointerstitial disease were clinically presented as CKD, mostly mild proteinuria, with or without microscopic hematuria, and also presented with hyperuricemia, urine glucose under normal blood glucose, anemia, polycystic kidneys. Only 1 case had a clear family history, and the diagnosis was mainly based on renal pathological characteristics and genetic testing. Compared with patients with non-genetic related tubulointerstitial lesion, patients with genetic tubulointerstitial disease had an earlier age of onset, higher blood uric acid, lower Hb and estiated glomemlar fitration (eGFR), and less edema and hypertension. Renal pathology of genetic tubulointerstitial disease presented tubular atrophy and interstitial fibrosis, abnormal tubular dilation, glomerular capsuledilation, and glomerular capillary loop shrinkage. Glomerular dysplasia and varying degrees of glomerular sclerosis were observed. Genetic tubulointerstitial disease patients were mainly treated with enteral dialysis, hypouricemic and hypoglycemic treatment. Two genetic tubulointerstitial disease patients had significantly deteriorated renal function, and 2 patients had stable renal function. CONCLUSIONS Patients with AKI or FS, who present serum immunofixation electrophoresis and/or serum free kappa light chain abnormalities, should be alert to LCCN or LCPT. Renal biopsy is a critical detection for diagnosis of LCCN and LCPT. Chemotherapy and stem cell transplantation could delay progression of renal function in patients with LCCN and LCPT. If the non-atrophic area of the renal interstitium presents glomerular capsule dilatation, glomerular capillary loop shrinkage, and abnormal tubular dilatation under the light microscopy, genetic tubulointerstitial disease might be considered, which should be traced to family history and can be diagnosed by genetic testing.
Humans ; Hematuria ; Immunoglobulin Light Chains/analysis* ; Multiple Myeloma ; Proteinuria ; Nephritis, Interstitial ; Acute Kidney Injury ; Anemia ; Renal Insufficiency, Chronic

BACKGROUND: Although the clinical importance of the immunological benefits of breastfeeding has been emphasized for decades, their direct relationship with acute pyelonephritis (APN) is still not clear. Our goal was to determine whether breastfeeding truly provides protection against APNs, while investigating the effects of other factors such as sex, age, mode of delivery, and birth weight on APN.METHODS: A total of 62 infants under 6 months of age who had both microbiologically and radiologically-confirmed APN were enrolled in the case group. Healthy infants (n = 178) who visited the hospital for scheduled vaccinations were enrolled in the control group. The following participant characteristics were compared between the case and control groups: age, sex, birth order among siblings, feeding methods, weight percentile by month, birth weight percentile by gestational age, gestational age at birth, and mode of delivery.RESULTS: Babies exclusively fed with manufactured infant formulae before 6 months of age had significantly higher risk for APN than breastfed or mixed-fed infants (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.687–7.031; P = 0.001). Firstborn babies had lower risk for APN than 2nd- or 3rd-born babies (OR, 0.43; 95% CI, 0.210–0.919). Other factors that increased the risk for APN were low birth weight percentiles (OR, 8.33; 95% CI, 2.300–30.166) and birth via caesarean section (OR, 2.32; 95% CI, 1.097–4.887). There were more preterm births in the case group (10.9% vs. 1.7%; P = 0.002), but this did not increase the risk for APN (OR, 4.47; P = 0.063).CONCLUSION: Feeding exclusively with formula before 6 months of age was related to higher risk for APN, which demonstrates that breastfeeding has a protective effect against APN. The other risk factors for APN were birth order (≥ 2nd-born), low birth weight, and birth via caesarean section.
Birth Order ; Birth Weight ; Breast Feeding ; Cesarean Section ; Feeding Methods ; Female ; Gestational Age ; Humans ; Infant Formula ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Parturition ; Pregnancy ; Premature Birth ; Pyelonephritis ; Reproductive History ; Risk Factors ; Siblings ; Urinary Tract Infections ; Vaccination

INTRODUCTION: Acute kidney injury (AKI) is one of the severe complications in dengue hemorrhagic fever, usually occurred in shock. We report an interesting case of AKI in a hemodynamically stable dengue hemorrhagic fever patient. CASE PRESENTATION: An 18-year-old male dengue fever patient referred to our institution in his day eight of illness due to three days of decreased urine output. He was hemodynamically stable with thrombocytopenia, increase in creatinine, positive for Anti dengue IgM, proteinuria, and hematuria. Ultrasound examination showed ascites. He was diagnosed with AKI stage III related to dengue hemorrhagic fever and underwent hemodialysis. A total of four series of hemodialysis and furosemide drip were performed during 12 days of admission and he was finally improved. CONCLUSION: Renal injury might occur in hemodynamically stable dengue hemorrhagic patients. It is a reversible condition; hence, appropriate treatment and close monitoring result in good outcomes
Severe Dengue ; Acute Kidney Injury ; Dengue ; Pyelonephritis ; Hemodynamics

PURPOSE: We investigated whether a renal size discrepancy on a renal sonogram (US) in children with febrile urinary tract infection (UTI) was correlated with the presence of cortical defects on their dimercaptosuccinic acid (DMSA) renal scan. METHODS: We examined 911 children who were admitted consecutively to our hospital with their first episode of febrile UTI from March 2001 to September 2014. All enrolled children underwent a US and DMSA scan during admission. According to the US findings, including the renal size discrepancy, data were compared between children with positive and negative DMSA scan results. A positive DMSA scan result was defined as reduced or absent tracer localization and indistinct margins that did not deform the renal contour. RESULTS: Mean renal lengths of the right and left kidneys were larger in children with positive DMSA scan results than in children with negative DMSA scan results (63.2±11.3 mm vs. 58.4±7.8 mm, P<0.001; 64.9±11.2 mm vs. 59.9±7.9 mm, P<0.001; respectively). A significant difference was observed in both renal lengths between children with positive and negative DMSA scan results (4.6±3.8 mm vs. 3.3±2.6 mm, P<0.001). A multiple logistic regression analysis, revealed that a small kidney, cortical thinning, and a renal length discrepancy on US findings were significant factors for predicting the presence of cortical defects on an acute DMSA scan [P=0.028, 95% confidence interval (CI) 1.054–2.547; P=0.004, 95% CI 1.354–4.810; P<0.001, 95% CI 1.077–1.190, respectively]. CONCLUSION: In conclusion, a renal size discrepancy on US findings in children with their first episode of febrile UTI was a helpful tool for predicting the presence of cortical defects on an acute DMSA scan.
Child ; Humans ; Kidney ; Logistic Models ; Pyelonephritis ; Succimer ; Urinary Tract Infections

OBJECTIVE: The purpose of the present study was to compare the diagnostic performance of initial procalcitonin, lactate, and high-sensitive C-reactive protein (hsCRP) for predicting bacteremia in female patients with acute pyelonephritis (APN). METHODS: We conducted a retrospective study of female APN patients who visited the emergency department (ED) at the studied hospital between January 2015 and December 2016. The main outcome was bacteremia, which was reported via the first blood culture at ED. The patient demographics, co-morbidities, physiologies, and laboratory variables including initial procalcitonin, lactate, and hsCRP levels, were collected and analyzed to identify associations with the presence of bacteremia. The area under the receiver operating curve (AUROC) and sensitivity (SE)/specificity (SP) were calculated for each variable. RESULTS: During the study period, 282 patients were enrolled. A total of 105 (37.2%) patients had bacteremia. Escherichia coli was the most frequent pathogen. The AUROC was 0.70 (0.63–0.76), 0.70 (0.63–0.76), and 0.56 (0.49–0.63) for the procalcitonin, lactate, and hsCRP, respectively. At a cut-off value of 0.163 ng/mL, the procalcitonin level predicted bacteremia, with a SE/SP of 95.2%/22.6%, respectively. At a cut-off value of 0.7 mmol/L, the lactate level predicted bacteremia with a SE/SP of 96.2%/20.9%, respectively. The combination of a procalcitonin level >0.447 ng/mL or a lactate level >0.7 mmo/L was chosen, as they showed 100% SE and a 100% negative predictive value. CONCLUSION: The initial serum procalcitonin and lactate levels showed similar and fair discriminative performance for predicting bacteremia in female APN patients, while the hsCRP level showed poor performance. The combination of procalcitonin and lactate (procalcitonin level≤0.447 ng/mL and lactate≤0.7 mmol/L) can be used to identify patients at low risk of bacteremia.
Bacteremia ; C-Reactive Protein ; Demography ; Emergency Service, Hospital ; Escherichia coli ; Female ; Humans ; Lactic Acid ; Pyelonephritis ; Retrospective Studies