https://www.ajkd.org/article/S0272-6386(97)90456-X/pdf

Histologic subclassification of IgA nephropathy: A clinicopathologic study of 244 cases

Hepatitis B infection and renal disease: clinical, immunopathogenetic and therapeutic considerations.

BACKGROUND The glomerular grading system is useful to compare biopsy specimens and to predict the natural course of disease in IgA nephropathy (IgAN), although no grading system can be perfect. METHODS H. S. Lee's grading system for IgAN was refined as follows: grade I, normal or focal mesangial cell proliferation; grade II, diffuse mesangial cell proliferation, or 75% of glomeruli with Cr/SS/GS. This refined H. S. Lee grading system was then tested for clinical relevance on 187 patients with IgAN followed up for an average of 6.5 years (minimum, 3 years). In the survival analysis, a modified primary end-point (progressive renal disease) was used. RESULTS The glomerular grades were significantly related to hypertension, serum creatinine levels and the amounts of proteinuria at time of biopsy. By univariate analysis, glomerular grades, hypertension, renal insufficiency and significant proteinuria (> or =1 g/day) were significantly associated with progressive renal disease. By multivariate analysis using the Cox regression model, glomerular grades, renal insufficiency and significant proteinuria were independent prognostic factors for progressive renal disease. At the end of follow-up, glomerular grades were significantly related to serum creatinine levels, amounts of proteinuria, hypertension and progressive renal disease. CONCLUSIONS These findings indicate that the refined H. S. Lee grading system for IgAN is useful in assessing the patients' clinical outcome and is sufficiently simple and easy to reproduce as to be universally applicable in prognostic work.

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Histological grading of IgA nephropathy predicting renal outcome: revisiting H. S. Lee's glomerular grading system

Systemically administered phosphorothioate antisense oligodeoxynucleotides can specifically affect the expression of their target genes, which affords an exciting new strategy for therapeutic intervention Earlier studies point to a major role of the liver in the disposition of these oligonucleotides The aim of the present study was to identify the cell type(s) responsible for the liver uptake of phosphorothioate oligodeoxynucleotides and to examine the mechanisms involved In our study we used ISIS-3082, a phosphorothioate antisense oligodeoxynucleotide specific for murine ICAM-1 Intravenously injected [3H]ISIS-3082 (dose: 1 mg/kg) was cleared from the circulation of rats with a half-life of 233+/-38 min At 90 min after injection (>90% of [3H]ISIS-3082 cleared), the liver contained the most radioactivity, whereas the second-highest amount was recovered in the kidneys (405+/-14% and 179+/-13% of the dose, respectively) Of the remaining tissues, only spleen and bone marrow actively accumulated [3H]ISIS-3082 By injecting different doses of [3H]ISIS-3082, it was found that uptake by liver, spleen, bone marrow, and kidneys is saturable, which points to a receptor-mediated process Subcellular fractionation of the liver indicates that ISIS-3082 is internalized and delivered to the lysosomes Liver uptake occurs mainly (for 561+/-30%) by endothelial cells, whereas parenchymal and Kupffer cells account for 396+/-45 and 43+/-17% of the total liver uptake, respectively Preinjection of polyinosinic acid substantially reduced uptake by liver and bone marrow, whereas polyadenylic acid was ineffective, which indicates that in these tissues scavenger receptors are involved in uptake Polyadenylic acid, but not polyinosinic acid, reduced uptake by kidneys, which suggests renal uptake by scavenger receptors different from those in the liver We conclude that scavenger receptors on rat liver endothelial cells play a predominant role in the plasma clearance of ISIS-3082 As scavenger receptors are also expressed on human endothelial liver cells, our findings are probably highly relevant for the therapeutic application of phosphorothioate oligodeoxynucleotides in humans If the target gene is not localized in endothelial liver cells, the therapeutic effectiveness might be improved by developing delivery strategies that redirect the oligonucleotides to the actual target cells

In vivo fate of phosphorothioate antisense oligodeoxynucleotides: predominant uptake by scavenger receptors on endothelial liver cells

Oxygen radicals and oxidatively modified proteins seem to participate in degenerative vascular and inflammatory diseases. Factors that contribute to the development of atherosclerosis, eg, oxidation of low-density lipoproteins (LDLs), may also contribute to glomerulosclerosis. Although the nature of the in vivo oxidants remains unknown, recent findings indicated that the myeloperoxidase (MPO)-H2O2-halide system could play an important role in modification of (lipo)proteins in human tissues. MPO, the enzyme responsible for hypochlorite (HOCl/OCl-) formation, is present in human atherosclerotic lesions and in inflammatory conditions. In the present study, MPO was identified by Western blot analysis and immunohistochemical technique in diseased human kidney either with primarily sclerotic or inflammatory lesions. Furthermore, the presence of HOCl-modified proteins was demonstrated in diseased renal tissues using a specific monoclonal antibody (clone 2D10G9), raised against HOCl-modified LDL, that does not cross-react with native LDL or Cu(2+)-, 4-hydroxynonenal-, or malondialdehyde-modified LDL. The antibody recognized HOCl-modified proteins in glomerular and tubulointerstitial inflammatory and fibrotic lesions and pronounced immunostaining was demonstrated in mononuclear cells. LDL or human serum albumin oxidized by HOCl in vitro, but not native LDL or human serum albumin, effectively competed with epitopes in diseased kidney for antibody binding. Western blot analysis in diseased kidney protein samples revealed at least two major proteins recognized by the anti-HOCl-modified protein monoclonal antibody. Densitometric evaluation of immunoreactive bands obtained under these conditions demonstrated that expression of HOCl-modified proteins is tightly coupled to expression of immunoreactive MPO in the same tissue samples. From our studies it is proposed that oxidation of proteins by HOCl might be a leading event in glomerular and tubulointerstitial injury. By this mechanism, mononuclear cells, a permanent source for MPO, may play a key role in the development of nephrosclerosis, glomerulo-clerosis, and tubulointerstitial fibrosis, respectively.

Immunological evidence for hypochlorite-modified proteins in human kidney.

https://www.kidney-international.org/article/S0085-2538(15)34509-9/pdf

Ultrastructural changes in IgA nephropathy in relation to histologic and clinical data.

Visualization of binding and uptake of oxidized low density lipoproteins by cultured mesangial cells.

https://www.kidney-international.org/article/S0085-2538(15)34388-X/pdf

A renal biopsy study of hepatitis B virus-associated nephropathy in Korea

https://www.ajkd.org/article/S0272-6386(88)80128-8/pdf

Acute Renal Failure Associated With Hematuria in IgA Nephropathy

Intratubular crystal deposition in transplanted patients is very rare and can be a cause of renal graft failure. Oxalate is a major component of the most common type of kidney stones, calcium oxalate stones. Hyperoxaluria is either inborn or acquired. Primary hyperoxaluria (PH) is a rare autosomal recessive disease resulting from deficiency of hepatic alanine:glyoxylate aminotransferase (AGT) (type I, PH-I) or glyoxylate reductase/D-glycerate dehydrogenase (type II, PH-II). Urinary excretion of both oxalate and glycolate is increased in PH-I, and that of both oxalate and L-glyceric acid is elevated in PH-II. PH results in urolithiasis and systemic oxalosis, often progressing to end-stage renal disease (ESRD) in young people. Late manifestations of PH-I are reported in a few middle-aged patients with recurrent renal stones or systemic oxalosis [1–3]. Recurrence of PH in renal transplants is common [4]. In a few patients, very rapid recurrence of disease has also been described [2]. Here, we report a case of late-onset PH-I, with the diagnosis being made only after transplantation presented with rapid intratubular calcium oxalate crystal deposition in a renal graft.

Haeng Il Koh

Papers

Ultrastructural changes in IgA nephropathy in relation to histologic and clinical data.

Visualization of binding and uptake of oxidized low density lipoproteins by cultured mesangial cells.

A renal biopsy study of hepatitis B virus-associated nephropathy in Korea

Acute Renal Failure Associated With Hematuria in IgA Nephropathy

Late-onset primary hyperoxaluria diagnosed after renal transplantation presented with early recurrence of disease