Independent associations of urine neutrophil gelatinase–associated lipocalin and serum uric acid with interstitial fibrosis and tubular atrophy in primary glomerulonephritis

Amornpan Lertrit,1 Suchin Worawichawong,2 Somlak Vanavanan,2 Anchalee Chittamma,2 Dittapol Muntham,3 Piyanuch Radinahamed,1 Aumporn Nampoon,4 Chagriya Kitiyakara1 1Department of Medicine, 2Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 3Section for Mathematics, Faculty of Science and Technology, Rajamangala University of Technology Suvarnabhumi, Phranakhon Si Ayutthaya, 4Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Abstract: The degree of interstitial fibrosis and tubular atrophy (IFTA) is one of the strongest prognostic factors in glomerulonephritis (GN). In experimental models, high serum uric acid (UA) could contribute to IFTA through direct effects on the renal tubules, but the significance of this process has not been evaluated in patients. Urine neutrophil gelatinase–associated lipocalin (NGAL) is produced by renal tubules following acute or chronic damage. We investigated the relationship between UA and NGAL excretion in primary GN and tested whether these biomarkers are independently associated with IFTA. Urine and blood were collected from patients on the day of kidney biopsy. IFTA was assessed semi-quantitatively. Fifty-one patients with primary GN were enrolled. NGAL/creatinine correlated significantly with proteinuria but not with glomerular filtration rate (GFR). By contrast, UA correlated with GFR but not with proteinuria. NGAL/creatinine did not correlate with UA. Both NGAL/creatinine and UA increased with the severity of IFTA. By multivariate analysis, GFR, NGAL/creatinine, and UA were independently associated with moderate-to-severe IFTA. Combining UA and NGAL/creatinine with classical predictors (proteinuria and GFR) tended to improve discrimination for moderate-to-severe IFTA. Findings that UA was unrelated to urinary NGAL excretion suggest that the two biomarkers reflect different pathways related to the development of IFTA in primary GN. Both NGAL/creatinine and UA were independently associated with moderate-to-severe IFTA. Keywords: biomarker, fibrosis, glomerulonephritis, kidney, neutrophil gelatinase–associated lipocalin, uric aci

Intestinal helminth infections and associated risk factors among adults in the Lao People's Democratic Republic

BACKGROUND: Helminthiases are highly endemic in Southeast Asia, including the Lao People's Democratic Republic (Lao PDR). This study aimed to assess the current intestinal helminth infections and the associated risk factors among adults across the Lao PDR. METHODS: A cross-sectional survey was conducted in 165 villages across 17 provinces and the Vientiane Capital, Lao PDR. A multi-stage sampling method was employed to select the adult study participants (>/= 18 years). Data collection included (1) interview of the study participants, (2) physical measurements, and (3) a five gram of stool sample from each study participant was collected and preserved in 10% formalin solution for intestinal helminth detection using formalin-ether concentration technique (FECT). Descriptive analysis was used to describe the socio-demographic characteristics of study participants and the prevalence of intestinal helminth infections. Logistic regressions were applied to test the association between intestinal helminth infection and individual risk factors. A P-value below 0.05 was considered statistically significant. RESULTS: A total of 2800 study participants were enrolled. Their average age was 46.0 years; 57.8% were female. Overall, 30.9%, 8.6% and 1.5% of study participants were infected with one, two, or three different intestinal helminth species, respectively. Among the study participants 21.6% were infected with hookworm, 18.8% with Opisthorchis viverrini-like (Ov-like) infection, 4.8% with Strongyloides stercoralis, 2.3% with Ascaris lumbricoides, 1.5% with Trichuris trichiura, and 3.3% with Taenia spp. Ov-like infection was of high prevalence in the southern (28.8%) and central (21.3%) provinces, while hookworm (26.3%), A. lumbricoides (7.3%), T. trichiura (3.1%), and Taenia spp. (4.2%) were prevalent in the northern provinces. Risk analysis showed that men were more likely to be infected with hookworm [adjusted odds ratio (aOR) = 1.2, P = 0.019]. The Lao-Tai ethnic group had a 5.2-times (P < 0.001) higher chance of having Ov-like infection than the minorities. Possession of toilet facility at home was associated with reduced odds for Ov-like (aOR = 0.4, P < 0.001) and hookworm (aOR = 0.6, P < 0.001) infections. CONCLUSIONS: Our study provides a nationwide update of the intestinal helminth prevalence among adults in Lao PDR. To the best of our knowledge, this is the first Lao nationwide survey on intestinal helminth infections and risk factors in adults. It provides crucial information for national control programs for intestinal helminth infections in Lao PDR

Dominant C3 glomerulopathy. new roles for an old actor in renal pathology

Recently, a number of reports have described dominant C3 deposits in renal biopsies of patients with infection-related glomerulonephritis (GN). While acute post-infectious GN and membranoproliferative GN are commonly characterized by immune deposits containing C3 and/or C4, the absence of immunoglobulin (Ig) and/or immune complexes at light or electron microscopy is a rather unusual observation. Dominant C3 deposition is believed to result from the alternative pathway of complement activation via the C3bBb “tickover” convertase. The actual occurrence of C3 glomerulopathy could be underestimated, since infection-related GN often quickly subsides without the need for a renal biopsy. A more thorough understanding of the pathways that lead to complement assembly and deposition within the kidney is needed to support a new classification of complement-related lesions, including entities such as dense deposit disease, (atypical) hemolytic-uremic syndrome, dominant C1q, CFHR5, C4d, and C3 glomerulopathies. We will briefly review recent work in this area, focusing on GN with selective complement C3 deposits