The association between renal function and neurological diseases in type 2 diabetes: a multicenter nationwide cross-sectional study

Background: The evidence for an association between renal function and neurological diseases among type 2 diabetes mellitus (T2DM) patients, particularly in the Asian population, is limited. This study aimed to assess the association between glomerular filtration rate (GFR) and various neurological diseases among T2DM patients in Thailand using a nationwide patient sample.

Methods: We conducted a nationwide cross-sectional study based on the DM/HT study of the Medical Research Network of the Consortium of Thai Medical Schools. This study evaluated adult T2DM patients receiving care at public Thailand hospitals in the year 2014. GFR was categorized into ≥60, 30–59, and < 30 mL/min/1.73 m². Neurological diseases studied included ischemic stroke/transient ischemic attack (TIA), hemorrhagic stroke, dementia, all cerebrovascular disease, and peripheral neuropathy. Multivariate logistic regression was performed to assess the association between GFR and neurological diseases.

Results: A total of 30,423 T2DM patients with available GFR data were included in the analysis. The mean GFR was 68.18 ± 26.45 mL/min/1.73 m². The prevalence of ischemic stroke/TIA, hemorrhagic stroke, dementia, any cerebrovascular diseases and peripheral neuropathy were 2.9%, 0.3%, 0.1%, 3.2%, and 3.1%, respectively. Patients with GFR of 30–59 and <30 mL/min/1.73 m² were significantly associated with increased rates of ischemic stroke/TIA, any cerebrovascular diseases, and peripheral neuropathy when compared with patients with GFR of ≥60 mL/min/1.73 m². This association remained significant after adjustment for potential confounders.

Conclusion: Decreased GFR was associated with increased ischemic stroke/TIA, all cerebrovascular diseases, and peripheral neuropathy. GFR should be monitored in diabetic patients for neurological disease awareness and prevention.     

Urine Periostin as a Biomarker of Renal Injury in Chronic Allograft Nephropathy

Background

Chronic allograft nephropathy (CAN) represents the main cause of renal allograft failure after transplantation. Noninvasive CAN testing is required. Periostin promotes the expression of a mesenchymal phenotype in renal tubules and is a promising urine biomarker for progressive renal injury. Information regarding periostin expression in the setting of CAN remains scarce.

Methods

Subjects were recruited from our outpatient transplantation clinic. Random urine samples were collected from CAN patients (n = 24) and renal transplant patients with normal renal function (transplant controls, n = 18). Control samples were collected from healthy volunteers (n = 18) who had normal renal function. Urine periostin was measured by enzyme-linked immunosorbent assay.

Results

The median urine periostin in CAN patients was significantly higher than in transplant and healthy controls (1.74 vs 0.00 vs 0.14 ng/mg creatinine, respectively; P < .001). Urine periostin enzyme-linked immunosorbent assay at a cutoff value of 0.152 ng/mg creatinine demonstrated the sensitivity, specificity, and accuracy for distinguishing CAN patients from transplant patients with normal renal function (91.7%, 77.8%, and 85.7%, respectively). In addition, urine periostin levels correlated directly with urine protein creatinine ratio (R = 0.566, P < .001) and serum creatinine (R = 0.522; P < .001), whereas inverse significant correlations were evidenced with estimated glomerular filtration rate (R = −0.431; P < .001).

Conclusion

The appearance of urine periostin in CAN patients but not in healthy and transplant controls underscores its value as a potential biomarker for chronic progressive renal injury in transplant recipients.     

Hematopoietic growth factor inducible neurokinin-1 (Gpnmb/Osteoactivin) is a biomarker of progressive renal injury across species

We sought to find a urinary biomarker for chronic kidney disease and tested hematopoietic growth factor inducible neurokinin-1 (HGFIN, also known as Gpnmb/Osteoactivin) as it was found to be a kidney injury biomarker in microarray studies. Here, we studied whether HGFIN is a marker of kidney disease progression. Its increase in kidney disease was confirmed by real-time PCR after 5/6 nephrectomy, in streptozotocin-induced diabetes, and in patients with chronic kidney disease. In the remnant kidney, HGFIN mRNA increased over time reflecting lesion chronicity. HGFIN was identified in the infarct portion of the remnant kidney in infiltrating hematopoietic interstitial cells, and in distal nephron tubules of the viable remnant kidney expressed de novo with increasing time. In vitro, it localized to cytoplasmic vesicles and cell membranes. Epithelial cells lining distal tubules and sloughed luminal tubule cells of patients expressed HGFIN protein. The urine HGFIN-to-creatinine ratio increased over time after 5/6 nephrectomy; increased in patients with proteinuric and polycystic kidney disease; and remained detectable in urine after prolonged freezer storage. The urine HGFIN-to-creatinine ratio compared favorably with the urine neutrophil gelatinase-associated lipocalin (NGAL)-to-creatinine ratio (both measured by commercial enzyme-linked immunosorbent assays (ELISAs)), and correlated strongly with proteinuria, but weakly with estimated glomerular filtration rate and serum creatinine. Thus, HGFIN may be a biomarker of progressive kidney disease.     

Urinary biomarkers of tubular injury to predict renal progression and end stage renal disease in type 2 diabetes mellitus with advanced nephropathy: A prospective cohort study

BackgroundNovel potential tubular biomarkers in diabetic nephropathy could improve risk stratification and prediction. The study aimed to evaluate the association of tubular damage markers with rapid renal progression and incidence of end stage renal disease (ESRD) in type 2 diabetes (T2DM).MethodsA prospective cohort study, involving a total of 257 patients with T2DM, was included. The baseline values of urine albumin, cystatin-C, angiotensinogen, kidney injury molecule-1 (KIM-1) and neutrophil-gelatinase associated lipocalin (NGAL) were measured. The composite outcomes included a rapid glomerular filtration rate (GFR) decline or incident of ESRD at 3-year follow-up.Main findingsThe composite outcomes were noted in 26.1%. Using univariate followed by multivariate COX proportional hazard regression analysis, the patients with highest quartiles of urine cystatin-C (HR 2.96, 95% CI, 1.38–6.35), urine angiotensinogen (HR 2.93, 95% CI, 1.40– 6.13) urine KIM-1 (HR 2.77, 95% CI, 1.27-6.05) and urine NGAL (HR 2.53, 95% CI, 1.11-5.76) were significantly associated with rapid renal progression when compared with the patients with the lowest quartiles of all tubular biomarkers.ConclusionsPatients with T2DM with high levels of baseline urine tubular biomarkers (cystatin-C, angiotensinogen, KIM-1 and NGAL) had a greater incidence of ESRD and rapid GFR decline.     

Pseudallescheria boydii brain abscess in a renal transplant recipient: first case report in Southeast Asia

Pseudallescheria boydii and its asexual form, Scedosporium apiospermum, are ubiquitous filamentous fungi that rarely cause central nervous system (CNS) infection. Brain abscess caused by P. boydii is a highly lethal infection, usually seen in organ transplant recipients who receive a number of immunosuppressive agents. We have presented a case of a 48-year-old man 6 years after renal transplantation who received methylprednisolone followed by antithymocyte globulin for treatment of acute cellular rejection. Eight weeks later, he developed fever, headache, and left-sided hemiparesis. Further investigation with magnetic resonance imaging of the brain showed multiple ring-enhancing hypodense lesions with marked edema which were compatible with brain abscesses. Following surgical drainage, multiple fungal elements were initially described as Aspergillus species. The patient failed to improve and died from rapidly progressive infection despite treatment with amphotericin B. Later a diagnosis was finally made by the isolation of P. boydii in pus culture. The specific diagnosis is difficult to rapidly make, because P. boydii mimics other fungi morphologically in tissue sections and may produce infections clinically similar to other mycoses. Culture of the organism is required for definitive diagnosis. P. boydii infections are important complications of transplantation. They are difficult to treat due to resistance to amphotericin B. Physicians should consider P. boydii a possible cause of brain abscess in organ transplant recipients, especially with heavy immunosuppressive agents. This is the first case report of CNS infection due to P. boydii in a renal transplant patient in Southeast Asia.