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Kidney Week

Abstract: FR-PO394

CKD of Unknown Etiology (CKDu) in Sri Lanka (SL): A Tissue Analysis

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Kambham, Neeraja, Stanford University, Stanford, California, United States
  • Nanayakkara, Nishantha, Teaching Hospital, Kandy, Kandy, Sri Lanka
  • Artiles, Karen L., Stanford University, Stanford, California, United States
  • Bhalla, Vivek, Stanford University, Stanford, California, United States
  • Fire, Andrew, Stanford University, Stanford, California, United States
  • Anand, Shuchi, Stanford University, Stanford, California, United States

Group or Team Name

  • CKDu Sri Lanka
Background

CKDu is a leading cause of kidney disease in Central & North Central SL. Based on a prospective renal biopsy study, we hypothesized that higher acuity reflects recent exposure to a putative toxin. Tissue evidence of hypothesized causes was sought in high acuity CKDu biopsies.

Methods

Forty-three patients had biopsy-confirmed CKDu (10/2016-9/2017); activity index (AI: tubulitis & interstitial inflammation in nonatrophic cortex) and chronicity index (CI: global glomerulosclerosis, periglomerular fibrosis, tubular atrophy, interstitial fibrosis) (scale 0-3) were scored. Thirteen biopsies met our definition of AI≥ 2 & CI ≤ 4 for active tubulointerstitial nephritis (AIN). A subset of AIN was analyzed for semiquantitative element content by mass spectrometry (MS) (n= 4) and electron microscopy (EM) (n=2). Non-CKDu SL biopsies were controls for histology (n=5) and MS (n=2).

Results

CKDu patients with AIN were 45 yrs old (mean; ±10.8), mostly men (75%), all born in endemic areas and drank well water as a primary source. Only 4 (33%) had dysuria, but 9 (75%) reported acute symptoms (fever, back/joint pain) within 6 mo prior to biopsy. None had hematuria, proteinuria was rare (8%) & mean sCr was 1.9 mg/dL. Rare silver stained dense granules visualized in tubular epithelial cells of both CKDu (67%) and controls (40%) corresponded to atypical lysosomes on EM. MS revealed no cadmium or arsenic; lead was minimal, lower than in control paraffin (Table). A high-throughput shotgun sequencing approach to detect infectious pathogens is underway.

Conclusion

We confirm an active phase in a subset of CKDu patients. Rare tubular atypical lysosomes were noted in both cases and controls. No lead, cadmium, or arsenic deposition was seen in the kidney. Further advanced tissue techniques may help elucidate causes of CKDu.

Content of select elements (of 70 analyzed) in SL Kidney Biopsies
Mean Content (ug/g)Paraffin (1)AIN (4)Controls (2)
Arsenic0.1060.2260.4325
Cadmium<0.001<0.001<0.001
Copper*2.11612.520.2805
Iron*25.02127.3<0.001
Lead1.8410.2952.108
Mercury<0.001<0.001<0.001
Nickel1.8291.778.01
Vanadium0.1120.3890.409

*Histochemical stains neg