Analysis of biopsy-proven nephrotic syndrome in Tibetan patients

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Analysis of biopsy-proven nephrotic syndrome in Tibetan patients

Nephrotic syndrome (NS)—a condition marked by excessive protein in urine (massive proteinuria) and low blood protein levels (hypoalbuminemia)—is a common kidney disorder worldwide. But until 2022, no research had focused on how NS affects Tibetans, a population with unique genetic and environmental factors from living at high altitudes. A study from Sichuan University’s West China Hospital changed that, offering the first comprehensive look at biopsy-proven NS in this understudied group.

Led by Rongshuang Huang, Jing Liu, Min Shi, Shenju Gou, Liang Ma, and Ping Fu from the hospital’s Kidney Research Institute, the research analyzed data from 122 Tibetan patients over 14 years old who underwent renal biopsies between 2009 and 2016. Researchers excluded patients with insufficient biopsy tissue, transplant kidney biopsies, or pregnancy to ensure accuracy. They used World Health Organization (WHO) standards to classify kidney diseases and applied standard statistical tests (like Student’s t-tests and chi-square) to analyze results, with a p-value below 0.05 considered statistically significant.

Who Were the Patients?

The average patient was 36.8 years old, and 57% were male. Key lab results showed:

  • Urine protein: 8.9 grams per 24 hours (range: 3.5–53.3 grams, well above the normal 0.15 grams or less).
  • Serum albumin: 21.2 grams per liter (normal: 35–50 grams per liter, indicating low blood protein).
  • Serum creatinine: 91.6 mmol/L (a marker of kidney function, within normal limits for most patients).

Common comorbidities included hypertension (32.8% of patients) and diabetes (7.4%).

Top Causes of NS in Tibetans

The study found membranous nephropathy (MN)—a type of primary glomerulonephritis (kidney disease starting in the kidneys)—was the leading cause of NS, affecting 34.3% of patients. Next was minimal change disease (MCD) (14.8%) and IgA nephropathy (IgAN) (12.3%), both also primary kidney conditions.

For secondary NS (caused by other diseases), diabetic nephropathy (DN) (from diabetes) and lupus nephritis (LN) (from lupus) each accounted for 7.4% of cases. Less common causes included:

  • Focal segmental glomerulosclerosis (FSGS) and membranoproliferative glomerulonephritis (MPGN) (4.1% each).
  • Hepatitis B virus-associated glomerulonephritis (HBVGN) (3.3%).
  • Rare conditions like Henoch–Schonelein purpura glomerulonephritis and sclerosing glomerulonephritis (2.5% each).

How Sex and Age Change NS Risk

The study revealed striking differences in NS causes by sex and age:

  • Sex: Females were more likely to have MCD (21.2% vs. 10% in males) and LN (11.5% vs. 4.3% in males). Males had a higher rate of DN (11.4% vs. 1.9% in females).
  • Age:
    • 14–24 years: MN and MCD tied as the top causes (25.8% each).
    • 25–44 years: MN remained the most common (41.5%), followed by LN (13.2%).
    • 45–59 years: MN was still top (31%), but DN (from long-term diabetes) became the second leading cause (20.7%).
    • 60+ years: MN (33.3%) and IgAN (22.2%) were the main causes.

Context: How Tibetans Compare to Other Populations

Previous research shows 19.1% of Tibetan adults have at least one sign of kidney damage—higher than other parts of China (Chen et al., 2011). While a 2014 study noted primary glomerulonephritis is common in Tibet, it included Han Chinese patients, making this new study the first Tibetan-only analysis.

The dominance of MN aligns with large Chinese studies but differs from regions like Hong Kong, Denmark, Korea, and Japan, where MCD is the top NS cause (Ng et al., 2018). The higher rate of DN (7.4%) compared to Beijing (0.72%) is notable, even though Tibetans have lower diabetes rates than Han Chinese. This suggests poor diabetes management in Tibetan patients with NS.

Interestingly, renal amyloidosis—a common NS cause in older adults—was not found, likely due to the small sample size.

Limitations to Consider

The study has two key limitations:

  1. Small sample size: 122 patients may not represent all Tibetans.
  2. Selection bias: Geographic distance and socioeconomic status may have excluded patients who couldn’t access the hospital for biopsies.

What This Means for Care

This first-of-its-kind study confirms that membranous nephropathy and minimal change disease are the main causes of biopsy-proven NS in Tibetans. The fact that NS causes vary by sex and age highlights the need for personalized care—for example, screening females for lupus or MCD and older males for diabetes-related kidney damage.

The study was published in the Chinese Medical Journal in 2022 by Rongshuang Huang, Jing Liu, Min Shi, Shenju Gou, Liang Ma, and Ping Fu from the Kidney Research Institute, Division of Nephrology, West China Hospital of Sichuan University.

doi.org/10.1097/CM9.0000000000001721

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