Osmotic Nephrosis and Acute Kidney Injury Associated With SGLT2 Inhibitor Use: A Case Report.

We report a case of a patient who developed dialysis-requiring acute kidney injury (AKI) after the use of canagliflozin. A 66-year-old man with type 2 diabetes who was recovering from left knee septic arthritis at a rehabilitation facility was admitted with oliguric AKI 5 days after starting treatment with canagliflozin, an inhibitor of sodium/glucose cotransporter 2 (SGLT2). The patient presented with hematuria, non-nephrotic-range proteinuria, and serum creatinine level of 6.8 (baseline, 1.1-1.3) mg/dL. There was no recent use of radiocontrast agents or exposure to other nephrotoxins. The patient subsequently required hemodialysis. Due to recent antibiotic use (ampicillin-sulbactam), acute interstitial nephritis was considered in the differential diagnosis. Kidney biopsy was performed, which showed the presence of osmotic nephropathy. The patient's kidney function returned to baseline after 2 weeks of hemodialysis. This case provides evidence of an association of osmotic nephropathy with the use of canagliflozin and discusses potential mechanisms. We recommend kidney biopsy for cases of severe AKI associated with SGLT2 inhibitors to better understand the relationship of this complication with the use of this class of medications.

Rapid direct identification of positive paediatric blood cultures by MALDI-TOF MS technology and its clinical impact in the paediatric hospital setting.

OBJECTIVE: Rapid diagnostic tools are imperative for timely clinical decision making, particularly in bacteraemic patients. This study evaluated the performance of a fast, inexpensive novel in house method for processing positive blood cultures for immediate identification of microorganisms by matrix-assisted laser desorption ionization-time of flight mass spectrometry (Vitek MS bioMérieux). We prospectively analyzed the clinical impact of such method on the management of pediatric patients. RESULT: In total, 360 positive blood cultures were included. Among 318 mono-microbial cultures, in-house method achieved correct identification in 270 (85%) cultures to the species level, whilst 43 (13.5%) gave no identification, and 7 (2.2%) gave discordant identifications. Identification of Gram-negative organisms was accurate to both species and genus level in 99% of isolates, and for Gram positives accuracy was 84% to genus and 81% to species level overall, with accuracy of 100% for Staphylococcus aureus and Enterococcus to the species level. Assessment of the potential impact of direct identification in sixty sequential cases revealed a clear clinical benefit in 35.5% of cases. Benefits included timely antibiotic rationalization, change of medical intervention, and early confirmation of contamination. This study demonstrates a highly accurate in-house method with considerable potential clinical benefits for paediatric care.

Homozygous splicing mutation in NUP133 causes Galloway-Mowat syndrome.

OBJECTIVE: Galloway-Mowat syndrome (GAMOS) is a neural and renal disorder, characterized by microcephaly, brain anomalies, and early onset nephrotic syndrome. Biallelic mutations in WDR73 and the 4 subunit genes of the KEOPS complex are reported to cause GAMOS. Furthermore, an identical homozygous NUP107 (nucleoporin 107kDa) mutation was identified in 4 GAMOS-like families, although biallelic NUP107 mutations were originally identified in steroid-resistant nephrotic syndrome. NUP107 and NUP133 (nucleoporin 133kDa) are interacting subunits of the nuclear pore complex in the nuclear envelope during interphase, and these proteins are also involved in centrosome positioning and spindle assembly during mitosis. METHODS: Linkage analysis and whole exome sequencing were performed in a previously reported GAMOS family with brain atrophy and steroid-resistant nephrotic syndrome. RESULTS: We identified a homozygous NUP133 mutation, c.3335-11T>A, which results in the insertion of 9bp of intronic sequence between exons 25 and 26 in the mutant transcript. NUP133 and NUP107 interaction was impaired by the NUP133 mutation based on an immunoprecipitation assay. Importantly, focal cortical dysplasia type IIa was recognized in the brain of an autopsied patient and focal segmental glomerulosclerosis was confirmed in the kidneys of the 3 examined patients. A nup133-knockdown zebrafish model exhibited microcephaly, fewer neuronal cells, underdeveloped glomeruli, and fusion of the foot processes of the podocytes, which mimicked human GAMOS features. nup133 morphants could be rescued by human wild-type NUP133 mRNA but not by mutant mRNA. INTERPRETATION: These data indicate that the biallelic NUP133 loss-of-function mutation causes GAMOS. Ann Neurol 2018;84:814-828.

Carotid artery diameter and wall stiffness in proteinuric renal disease without severely reduced kidney function.

PURPOSE: To evaluate the carotid artery diameter, and wall thickness and stiffness in patients with glomerulopathy and proteinuria without severely reduced kidney function. METHODS: We compared 30 control subjects to 30 patients with glomerular disease, proteinuria, and glomerular filtration rate > 30 ml/min/1.73 m(2) : membranous glomerulonephritis (n = 13), minimal change disease (n = 2), focal and segmental glomerulosclerosis (n = 3), IgA nephropathy (n = 5), lupus nephritis (n = 5), antiphospholipid antibody nephropathy (n = 1), cryoglobulinemic glomerulonephritis (n = 1). The laboratory evaluations included carotid artery diameter, intima-media thickness, and stiffness measurements. RESULTS: Carotid cross-sectional area of intima-media complex was thicker in patients (18.6 ± 1.4 [x ± SEM]) than in controls (14.8 ± 0.6 mm(2) , p = 0.014), as was carotid artery wall stiffness (8.96 ± 0.86 versus 5.65 ± 0.38, [x ± SEM], p < 0.01). This difference remained significant after adjustment for age, sex, and metabolic cardiovascular risk factors: carotid stiffness was 9.19 ± 0.67 (99% confidence interval [CI] 7.40-10.98)] in patients and 4.80 ± 0.75 (99% CI 2.79-7.11) in controls; adjusted mean difference 4.40 (99% CI 1.46-7.34); p <0.001. CONCLUSIONS: This study showed, for the first time, signs of altered structural and elastic properties of the arterial wall in patients with proteinuria and glomerular disease without severely reduced kidney function.

Identification of a novel de novo GATA3 mutation in a patient with HDR syndrome.

We describe the case of a 21-year-old male with hypocalcaemia, hyperphosphataemia, recurrent limb twitch, deafness, proteinuria, increased serum creatinine and urea nitrogen levels, and shrinkage of both kidneys. Brain computed tomography showed intracranial calcifications. The patient was diagnosed with hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) syndrome. DNA sequence analysis of the GATA3 gene showed a novel de novo mutation, c. 529dupC (p. Arg177profs*126), in exon 2, resulting in a frameshift mutation with a premature stop codon after a new 126 amino acid sequence. We provide further evidence that HDR syndrome is caused by haploinsufficiency of GATA3.

[Ultrasonographic finding and treatment of a cow with pyelonephrosis]. / Sonographische Befunde und Therapie bei einer Kuh mit Pyonephrose.

Ultrasonography of a six-year-old Simmental cow revealed an abscess like structure, approximately 15 cm in diameter, in place of the right kidney. The cow had a history of colic for 4 days and was referred to our clinic with a tentative diagnosis of caecal dilatation. The cow voided dark opaque urine with white floccules. Laboratory examination yielded increased haematocrit, leukocytosis with left shift, hyperbilirubinaemia and azotaemia. The diagnosis was confirmed, the caecum emptied surgically and the pus-filled structure at the site of the right kidney removed. A diagnosis of pyonephrosis was made after pathological examination of the pus-filled structure.

Imaging findings of spontaneous bilateral renal artery dissection.

Bilateral spontaneous renal artery dissection is extremely rare with computed tomography angiography being an efficient noninvasive alternative to catheter angiography for its diagnosis. We report the case of a 65-year-old woman with bilateral spontaneous renal artery dissection resulting in bilateral renal infarctions and hydroureteronephrosis.

Non-contrast computed tomography after percutaneous nephrolithotomy: findings and clinical significance.

OBJECTIVE: To describe the post-percutaneous nephrolithotomy (PNL) non-contrast-enhanced computed tomography (NCCT) findings and assessed their clinical significance. NCCT evaluates stone clearance after PNL and also reveals procedure-related changes. METHODS: One hundred consecutive patients who underwent PNL were evaluated by NCCT one day post-procedure. Two radiologists analyzed the type and severity of the NCCT findings, which were then statistically analyzed in relation to the patient's clinical course. RESULTS: The patients' mean age was 54 years (range 18-82) and the mean maximal stone diameter was 37 mm (range 15-70). The median operative time was 110 minutes for an immediate stone-free rate of 83%, changing to 94% (P = .073) after a second-look PNL in 11 patients. The post-PNL NCCT findings were hydronephrosis (70%), atelectasis (54%), ipsilateral pleural effusion (52%), paracolic gutter fluid (44%), perinephric hematoma (40%), perinephric fluid (32%), ureteronephrosis (31%), renal swelling (23%), contralateral pleural effusion (22%), residual fragments (RFs) (17%), subcapsular hematoma (10%), and flank hematoma (6%). Univariate analysis revealed a significant association with clinical variables for all NCCT findings except for atelectasis, ureteronephrosis, contralateral pleural effusion, RFs, and flank hematoma. In multivariate analysis, only perinephric fluid (P = .007) and ipsilateral pleural effusion (P = .034) were associated with longer hospitalization, and perinephric fluid with longer recovery (P = .004). The complication rate was 12%, but none were linked with the radiological findings. CONCLUSION: This work describes the post-PNL NCCT findings and their clinical significance. Perinephric fluid and ipsilateral pleural effusion were found to independently predict longer hospitalization and recovery time.

[Classification of hydroureteronephrosis by ultrasonography findings].

A complex examination including blood and urine biochemistry, pyelomanometry, x-ray-radionuclide and endoscopic investigations of the urinary tract as well as ultrasonography with estimation of morphometric and functional parameters of different parts of the urinary tract was conducted in 525 patients with various diseases of the pelvic ureter and urinary bladder complicated by hydroureteronephrosis (HUN) and 50 healthy controls. The findings made it possible to distinguish four stages of HUN: hyperkinetic, dyskinetic, hypokinetic and akinetic. This gradation rests on the results of sonographic assessment of morphofunctional condition of the urinary tract which were compared with findings of the other methods of urological examination. The proposed 4-stage HUN classification based finally only on ultrasonography data describes not only severity of anatomic changes but, indirectly, functional reserves of the upper urinary tract. Sonography is an available, non-invasive, cost-effective method without contraindications. This allows recommendation of this HUN classification for wide application. According to the stage of urodynamic disorder, therapeutic policy is proposed.

Galloway-Mowat syndrome: prenatal ultrasound and perinatal magnetic resonance imaging findings.

OBJECTIVE: To present prenatal ultrasound and perinatal magnetic resonance imaging (MRI) findings of Galloway-Mowat syndrome. CASE REPORT: A 31-year-old woman, gravida 3, para 2, was referred for genetic counseling at 29 weeks of gestation because of abnormal ultrasound findings and a previous child with Galloway-Mowat syndrome. During this pregnancy, microcephaly, intrauterine growth restriction (IUGR), and oligohydramnios were first noted at 27 weeks of gestation. Repeated ultrasounds showed microcephaly, IUGR, and oligohydramnios. MRI performed at 32 weeks of gestation showed reduced sulcation of the brain, pachygyria, poor myelination of the white matter, and cerebellar atrophy. A diagnosis of recurrent Galloway-Mowat syndrome was made. At 40 weeks of gestation, a 2,496-g female baby was delivered with microcephaly, a narrow slopping forehead, epicanthic folds, microphthalmos, a highly arched palate, a small midface, a beaked nose, thin lips, large low-set floppy ears, clenched hands, and arachnodactyly. Postnatal MRI findings were consistent with the prenatal diagnosis. Renal ultrasound showed enlarged bilateral kidneys with increased echogenicity. At the age of 2 weeks, the infant became edematous and developed nephrotic syndrome. CONCLUSION: Microcephaly, IUGR, and oligohydramnios are significant ultrasound triad of fetal Galloway-Mowat syndrome. Prenatal ultrasound diagnosis of microcephaly, IUGR, and oligohydramnios in late second trimester or in early third trimester should alert clinicians to the possibility of Galloway-Mowat syndrome and prompt a detailed search of abnormal sulcation, cortical gyral maldevelopment, and cerebellar atrophy by fetal ultrafast MRI.

Localised retroperitoneal amyloidosis mimicking retroperitoneal fibrosis: a rare cause of obstructive uropathy.

Primary localised amyloidosis involving the retroperitoneum is a rare disease. We report a 71-year-old diabetic man who presented with generalised fatigue, malaise and elevated serum creatinine. Investigations confirmed obstructive uropathy secondary to a retroperitoneal mass behind the urinary bladder, causing extrinsic compression of both the ureters, resulting in bilateral hydroureteronephrosis. Following initial bilateral percutaneous nephrostomies to stabilise renal function, a computed tomography-guided biopsy of the pelvic lesion which was done, was suggestive of amyloidosis. We present this case due to the rarity of localised retroperitoneal amyloidosis as a cause of obstructive uropathy.

Chronic kidney disease with three cases of oxalate-like nephrosis in Ragdoll cats.

Two unrelated Ragdoll cat mothers in Norway were found dead from renal disease. The histopathology was consistent with oxalate nephrosis with chronic or acute-on-chronic underlying kidney disease. Both cats had offspring and relatives with signs of urinary tract disease, including a kitten dead with urethral gravel. Eleven living Ragdoll cats, including nine relatives of the dead cats and the male father of a litter with similarly affected animals, were tested for primary hyperoxaluria (PH) type 1 and 2 by urine oxalate and liver enzyme analysis. Renal ultrasound revealed abnormalities in five living cats. One of these was azotaemic at the time of examination and developed terminal kidney disease 9 months later. A diagnosis of PH was excluded in 11 cats tested. The inheritance and aetiological background of the renal disease present in the breed remains unresolved at this point in time.

The ACTIVE Trial: comparison of the effects on renal function of iomeprol-400 and iodixanol-320 in patients with chronic kidney disease undergoing abdominal computed tomography.

BACKGROUND: We performed a multicenter, double-blind, randomized, parallel-group study to compare the renal effects of iomeprol-400 and iodixanol-320 in patients with preexisting chronic kidney disease undergoing contrast-enhanced multidetector computed tomography of the liver. METHODS: One hundred forty-eight patients with moderate-to-severe chronic kidney disease, ie, serum creatinine (SCr) > or =1.5 mg/dL (132.6 micromol/L) and/or calculated creatinine clearance (CrCl) <60 mL/min, undergoing contrast-enhanced multidetector computed tomography of the liver were randomized to equi-iodine doses (40 gI) of either the low-osmolar agent iomeprol-400 (400 mgI/mL, 726 mOsm/kg, N = 76) or the isotonic agent iodixanol-320 (320 mgI/mL, 290 mOsm/kg, N = 72), injected intravenously at 4 mL/S, followed by a bolus of 20 mL normal saline solution at the same rate. SCr was obtained at screening, baseline and at 48 to 72 hours postdose. SCr measurements and CrCl calculations were performed by a central laboratory. Contrast-induced nephropathy (CIN) was defined as an absolute SCr increase of > or =0.5 mg/dL (44.2 micromol/L) from baseline to 48 to 72 hours postdose. Mean SCr changes from baseline were also assessed. A Renal Safety Review Board comprised 3 medical experts reviewed the renal safety data, demographics, medical history, CIN risk factors, concomitant medications, and hydration status of each subject in a blinded manner. RESULTS: The 2 study groups were comparable with regard to age, gender distribution, concomitant nephrotoxins, hydration status, and total iodine dose; however, the iomeprol-400 group showed a significantly higher proportion of patients with diabetes mellitus (P = 0.02). Baseline SCr was 1.7 +/- 0.6 mg/dL (150.3 +/- 53.0 micromol/L) in the iomeprol-400 group and 1.7 +/- 0.7 mg/dL (150.3 +/- 61.9 micromol/L) in the iodixanol-320 group (P = 0.87). Predose CrCl was 41.5 +/- 13.1 mL/Min in the iomeprol-400 group and 43.0 +/- 13.3 mL/Min in the iodixanol-320 group (P = 0.49). Five of 72 patient receiving iodixanol-320 (6.9%) and none of the patients receiving iomeprol-400 showed an increase of > or =0.5 mg/dL (44.2 micromol/L) from baseline [P = 0.025, 95% CI (-12.8%, -1.1%)]. The mean SCr change from baseline was significantly higher (P = 0.017 ANCOVA) after iodixanol-320 (0.06 +/- 0.27) than after iomeprol-400 (-0.04 +/- 0.19). CONCLUSIONS: The incidence of CIN was significantly higher after IV administration of iodixanol-320 than iomeprol-400. The mean rise in SCr from baseline was also higher in patients receiving iodixanol.

Percutaneous ureterostomy as an effective diversion in a newborn.

Ectopic ureter in a duplicated system in men is rare and rarely causes bilateral obstructive symptoms. The tendency of the ureter to dilate more than the caliceal system is unique to neonates and makes upper urinary diversions more challenging. However, alternative percutaneous diversions other than nephrostomy might be beared in mind in such cases with huge dilatation in ureters in suffering neonates. As discussed in this case percutaneous ureterostomy may be very effective and have a role in diagnosis and management of neonatal hydroureteronephrosis.

Use of iso-osmolar nonionic dimeric contrast media in multidetector row computed tomography angiography for patients with renal impairment.

OBJECTIVES: We wanted to determine the rate of contrast-induced nephropathy (CIN) caused in patients with renal impairment undergoing multidetector row computed tomography (MDCT) angiography with intravenous administration of iso-osmolar dimeric contrast media (iodixanol). MATERIALS AND METHODS: The first consecutive 100 patients referred to CT with a serum creatinine level (SCr) between 1.5 and 6 mg/dL were enrolled in the study. Serum creatinine also was determined on days 3 and 7 after the intravenous administration of 100 mL of iodixanol 270 with 5 mL/s. A CIN was considered if variation of SCr on day 3 was >0.5 mg/dl above baseline. RESULTS: Nine patients developed a CIN after MDCT angiography; 7 of them recovered completely by day 7, and the remaining 2 showed elevated SCr on day 7 but did not develop renal failure during their hospital stay. CONCLUSIONS: MDCT angiography performed in patients with impaired renal function with iodixanol may result in CIN but complete recovery is probable.

Sliding hernia containing the ureter--a rare cause of graft hydroureteronephrosis: a case report.

Obstructive uropathy following renal transplantation is frequently reported. However, ureteral obstruction due to its incorporation in a sliding hernia is a rare event. Herein, we report a case of late graft hydroureteronephrosis secondary to a sliding hernia containing the transplanted ureter. The diagnosis was confirmed with the aid of magnetic resonance urography and antegrade urography. Following hernioplasty, a decrease of serum creatinine level was achieved with significant decompression of the system.

Pelvocalyceal thickening in HIV-associated nephropathy.

BACKGROUND: Previously reported causes of renal pelvocalyceal thickening (PCT) include infection, acute tubular necrosis and obstruction. This study was performed to evaluate the significance of PCT noted sonographically in patients with hyperechoic native kidneys. METHODS: We evaluated sonograms of 178 consecutive patients with hyperechoic native (excluding small and hydronephrotic) kidneys for the presence of PCT, and reviewed medical charts of patients with this finding. We also reviewed sonograms of two control groups: 20 consecutive patients with nephrosis unrelated to human immunodeficiency virus (HIV) infection who underwent renal biopsy, and 30 consecutive patients with severe hypoalbuminemia unrelated to kidney disease. RESULTS: PCT was observed in 20 study patients with hyperechoic kidneys. HIV-associated nephropathy (HIVAN) was diagnosed in 15 patients (14 with bilateral PCT) in whom previously reported causes of this appearance were excluded. PCT was not observed in control patients. CONCLUSION: Renal PCT can occur in patients with HIVAN in the absence of HIV-related complications. PCT in HIVAN does not merely reflect nonspecific nephrosis or hypoalbuminemia. HIVAN should be considered if PCT is noted sonographically in hyperechoic kidneys, even in patients not clinically suspected of harboring HIV infection.

Prenatal diagnosis of congenital nephrosis of the Finnish type (CNF) in the second trimester.

Congenital nephrosis of the Finnish type is an hereditary, autosomal recessive disease which leads to death in early infancy. This is a case report concerning an affected fetus with legal interruption in the 24th week of gestation on the basis of certain sonographic changes in the fetal kidneys and changes in the protein profile in amniotic fluid, which were consistent with nephrotic damage of the kidneys. Light and electron microscopy showed evidence of CNF, i.e. increase of mesangial matrix and cells in glomeruli, dilated tubular segments, and effaced and plumb foot-processes of the glomerular epithelial cells. Antenatal diagnosis of CNF therefore seems feasible in the second trimester of gestation by means of AFP determinations in maternal serum and amniotic fluid as well as by using sonographic criteria and determination of proteins in amniotic fluid.