Apoptosis and loss of renal tissue in polycystic kidney diseases
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1Department of Medicine, University of California at Los Angeles 90024-1689, USA.
Background:
Polycystic kidney disease is characterized by the enlargement of renal cysts, interstitial fibrosis, and gradual loss of normal renal tissue in association with progressive deterioration of renal function. The process causing the progressive loss of renal tissue is unknown, but it could be the result of a form of programmed cell death known as apoptosis.
Methods:
We assayed apoptotic DNA fragmentation in normal and polycystic kidneys biochemically by gel electrophoresis and histochemically by in situ end-labeling. A DNA-specific dye, Hoechst 33258, was used to detect morphologic apoptosis in renal samples from patients with normal kidneys, polycystic kidney disease, and other kidney diseases.
Results:
Apoptotic DNA fragmentation was detected in polycystic kidneys from 5 patients without renal failure and 11 patients with renal failure but not in kidneys from 12 patients with no renal disease. In situ end-labeling revealed apoptotic cells in glomeruli, in cyst walls, and in both cystic and noncystic tubules of the polycystic kidneys. No tubular apoptosis was detected in renal-biopsy specimens from five patients with IgA nephropathy, three patients with nephrosclerosis, two patients with focal glomerulosclerosis, one patient with diabetic nephropathy, six patients with acute tubular necrosis, or four patients with acute and four patients with chronic renal-transplant rejection. The capacity of polycystic kidney cells to undergo apoptosis was retained in vitro in the absence of uremia, ischemia, and other confounding pathologic conditions.
Conclusions:
Apoptotic loss of renal tissue may be associated with the progressive deterioration of renal function that occurs in patients with polycystic kidney disease.
Insights
Polycystic kidney disease (PKD) involves renal cyst enlargement and tissue loss. This study found evidence of programmed cell death (apoptosis) in PKD kidneys, suggesting it contributes to kidney function decline.
Area of Science:
- Nephrology
- Cell Biology
- Pathology
Background:
- Polycystic kidney disease (PKD) is marked by renal cyst enlargement, fibrosis, and declining kidney function.
- The mechanism behind progressive renal tissue loss in PKD remains unclear.
- Apoptosis, a form of programmed cell death, is a potential contributor to this tissue loss.
Purpose of the Study:
- To investigate the presence and role of apoptosis in the pathogenesis of polycystic kidney disease.
- To determine if apoptotic DNA fragmentation occurs in kidneys affected by PKD.
Main Methods:
- Biochemical assays (gel electrophoresis) and histochemical techniques (in situ end-labeling) were used to detect apoptotic DNA fragmentation.
- A DNA-specific dye (Hoechst 33258) identified morphologic apoptosis in renal samples.
- Apoptosis was assessed in kidneys from patients with PKD, normal kidneys, and kidneys with other renal diseases.
Main Results:
- Apoptotic DNA fragmentation was detected in polycystic kidneys from patients with and without renal failure.
- In situ end-labeling confirmed apoptotic cells in glomeruli, cyst walls, and tubules of PKD kidneys.
- No tubular apoptosis was observed in kidneys with other renal diseases, and PKD cells retained apoptotic capacity in vitro.
Conclusions:
- Apoptosis is present in polycystic kidneys and may contribute to the progressive loss of renal tissue.
- The findings suggest that apoptotic loss of renal tissue is associated with the decline in renal function observed in PKD patients.