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- Bakoush, Omran
(författare)
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Diagnostic and prognostic value of proteinuria in chronic renal diseases
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- To the extent that increased urinary protein excretion is an indicator of alterations of the glomerular capillary wall (GCW) and appearance of tubulointerstitial damage, proteinuria can be a good marker of the overall severity of the glomerular and tubulointerstitial damage, and therefore, the prognosis of glomerular diseases. Studies I, II, and III show that it is the type of proteinuria, rather than the degree of albuminuria, that predicts the progression in renal, proteinuric diseases. For instance, we found that the quantity of urinary IgM correlated to the decrease of glomerular filtration rate (GFR) in primary glomerular diseases,irrespective of the degree of albuminuria. 21% of patients with initial proteinuria with high IgM content developed end-stage renal failure compared to none of the patients with proteinuria with low IgM content. Patients who maintained high urinary IgM excretion during the course of glomerular disease showed a more rapid GFR decline over time compared to patients with maintained low IgM excretion despite persistent high degree of albuminuria. Changes in urinary IgG, but not in albumin excretion, during the course of the glomerular disease, correlated to changes in urinary protein HC excretion. Protein HC is a marker of impairment of the proximal tubular function. In study IV, we observed that patients with type 2 DN had a higher urinary excretion of high molecular weight proteins (IgG and IgM) than patients with type 1 DN, despite similar degree of albuminuria. This suggests partly different patho-physiological mechanisms in diabetic nephropathy (DN) in type 1 and type 2 diabetes mellitus. Patients with type 2 DN have a better preserved ratio of urinary excretion of IgG2/IgG4 than type 1 DN patients, indicating that the charge selectivity is less impaired in type 2 DN. Finally, old but not young hypertensive rats (study V) develop proteinuria as a result of a dysfunction of the glomerular capillary filter, affecting primarily its size-selectivity. The changes are functionally compatible with the appearance in the glomerular barrier of an increased number of unselective pores. Conclusions: During the course of glomerular diseases a maintained low urinary excretion of IgG or IgM indicates a salutary prognosis. Different patho-physiological mechanisms of albuminuria in type 1 and type 2 diabetes have been found, and hypertension induced proteinuria is primarily a size-selective disorder.
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- Bakoush, Omran, et al.
(författare)
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Effect of diabetes mellitus on the recovery of changes in renal functions and glomerular permeability following reversible 24-hour unilateral ureteral obstruction
- 2018
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Ingår i: Journal of Diabetes. - : Wiley. - 1753-0393 .- 1753-0407.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Following reversal of short periods of ureteral obstruction (UO), glomerular and tubular renal dysfunction recovers with time. Diabetes mellitus (DM) affects glomerular function; thus, the ability of diabetic kidneys to recover from UO may be impaired. This study investigated the effects of long-term DM on the recovery of glomerular and tubular function, as well as permeability of the glomerular filtration barrier (GFB), after unilateral UO (UUO) reversal. Methods: Diabetes mellitus was induced in Wistar rats by intraperitoneal streptozotocin. All diabetic and age-matched control rats underwent reversible 24-hour left UUO. The renal function of both kidneys was measured using clearance techniques 3 hours and 7 and 30 days after UUO reversal. Glomerular permeability was assessed by measuring the glomerular sieving coefficients for fluorescein isothiocyanate-conjugated Ficoll (molecular radius: 20-90 Å). Results: Unilateral UO induced transient changes in the size selectivity of GFB small pores. However, the size selectivity function of large pores had not returned to baseline even 30 days after UUO reversal. Diabetes mellitus caused exaggerated early alterations in glomerular hemodynamic and tubular function, as well as size selectivity dysfunction of both small and large pores. At 30 days after UUO reversal, despite glomerular hemodynamic and tubular function and the size selectivity of small pores returning to normal in both diabetic and non-diabetic rats, the residual size selectivity dysfunction of large pores was more severe in diabetic rats. Conclusion: Unilateral UO caused long-term dysfunction in the size selectivity of large pores of the GFB. In addition, DM significantly exaggerated this dysfunction, indicating a more ominous outcome in diabetic kidneys following UUO.
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- Bakoush, Omran, et al.
(författare)
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High proteinuria selectivity index based upon IgM is a strong predictor of poor renal survival in glomerular diseases
- 2001
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 16:7, s. 1357-1363
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The transport of large proteins across the glomerular capillary wall (GCW) may increase several fold in glomerular diseases. The occurrence of IgM in urine is a consequence of the presence of large defects or shunts in the GCW, whereas albuminuria is probably a result of an altered charge- and size-selectivity of the GCW. In order to examine whether patho-morphological differences influence the renal outcome in proteinuric glomerulopathies, we examined urinary excretion of IgM and albumin as prognostic markers of glomerular disease. METHODS: An observational study over a median of 41 (+/-3) months was conducted in 84 patients with biopsy-verified glomerular disease. The patients were subdivided into groups with low (< or =0.002) and high (>0.002) proteinuria selectivity index based upon IgM (IgM-SI), and into groups with low (< or =200 mg/mmol) and high (>200 mg/mmol) albumin creatinine index (ACI). RESULTS: In the high IgM-SI group, the median creatinine clearance (Ccr) decreased by 26%, and 62% of the patients decreased in Ccr by >5 ml/ min/year during the follow-up time. In comparison, the median Ccr decreased by 8% in the low IgM-SI group (P<0.001) and only 18% of the patients in this group deteriorated by >5 ml/min/year in the Ccr. Eleven (21%) of the 51 patients in the high IgM-SI group developed end-stage renal failure compared with none of the 33 patients in the low IgM-SI group. All the patients that progressed to uraemia had decreased Ccr (<60 ml/min) at entry into the study. However, among all these patients, only those with high IgM-SI, and none with low IgM-SI, developed end stage renal failure. The fall in Ccr did not differ significantly between the patients in high (12%) and low (16%) ACI groups. CONCLUSION: The results of this study indicate that an increased IgM-SI value is a stronger predictor of clinical outcome in proteinuric glomerulopathies than baseline albuminuria. This finding may reflect different patho-histological mechanisms influencing renal survival in glomerular diseases.
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- Bakoush, Omran, et al.
(författare)
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Higher urinary IgM excretion in type 2 diabetic nephropathy compared to type 1 diabetic nephropathy.
- 2002
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 61:1, s. 203-208
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Proteinuria, due to impairment of the charge- and/or size selectivity of the glomerular capillary wall (GCW) is the earliest clinical evidence of diabetic nephropathy (DN). To study the pathophysiological differences between patients with DN in type 1 diabetes mellitus (type 1 DN) and type 2 diabetes mellitus (type 2 DN), we compared the patterns of urinary proteins of different size and charge in the two entities of diabetic kidney disease. METHODS: Urine concentrations of albumin, IgG2, IgG4 and IgM were assessed in 22 (15 males and 7 females) patients with type 1 DN, and in 20 (18 males and 2 females) patients with type 2 DN. Comparisons with one control group of 13 (12 males and one female) patients with nephrosclerosis due to systemic hypertension and a second control group of 16 (14 males and 2 females) healthy controls were made. RESULTS: The urine excretion of IgG2 and IgM and the ratio of IgG2 to IgG4 (IgG2/IgG4), were significantly higher in type 2 DN compared to type 1 DN (P < 0.01). Patients with type 2 DN and patients with nephrosclerosis had significantly higher urine excretion of IgG and IgM compared to the age-matched healthy subjects (P < 0.001). The IgG2/IgG4 ratio was higher in type 2 DN compared to nephrosclerosis and healthy controls (P < 0.01). CONCLUSION: The increased urine excretion of IgG and IgM that accompanies albuminuria in type 2 DN suggests that the dominant pathophysiological mechanism of proteinuria in type 2 DN might be an alteration of the size selective properties of the glomerular capillary wall, including the occurrence of non-discriminatory "shunt pathways." The charge selective properties of the glomerular capillary wall seem to be intact in type 2 DN, as indicated by the high IgG2/IgG4 ratio. The mechanisms of proteinuria in type 1 DN seem to be merely a consequence of an impaired charge selectivity of the glomerular capillary wall.
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- Bakoush, Omran, et al.
(författare)
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Inaccuracy of GFR predictions by plasma cystatin C in patients without kidney dysfunction and in advanced kidney disease.
- 2008
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Ingår i: Clinical Nephrology. - 0301-0430. ; 69:5, s. 331-338
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In clinical practice there is need for a simple and reliable test for determination of impaired renal function. With reductions in GFR, the plasma cystatin C concentration (C, mg/l) will increase earlier than serum creatinine, and it is generally agreed that plasma cystatin C is only little affected by body weight, age or sex. However, some reports indicate that cystatin C may be influenced not only by GFR, but also by malignancy, inflammation and high doses of corticosteroids. The aim of the present study was to investigate how plasma cystatin C predicts GFR in distinct subcategories of patients with various disorders as well as in organ transplant patients. METHODS: Plasma cystatin C was measured in 536 patients (age range 0.3-96 years, 262 females, 274 males), consecutively referred to our hospital for determination of GFR by iohexol clearance. Correlations of log GFR vs. log cystatin C were used to compare plasma cystatin C and measured GFR for the following categories: individuals with no known kidney disease (No-KD), malignant patients with (mostly) normal GFR, solid organ-transplanted patients, and patients with native chronic kidney disease (CKD). RESULTS: In patients with normal kidney function and cystatin C level GFR>30 ml/min(-1) (1.73 m2)(-1)) or solid organ transplantation (GFR=84.55 C(1.7666) and GFR=83.95(C-1.5968), respectively). CONCLUSION: Therefore, for these categories, a common equation for all patients with increased cystatin C, irrespective of cause of renal impairment, could be used, namely that presented by Grubb et al. [2005] (GFR=83.93(C-1.676)). However, at marked reductions of renal function (GFR<30 or cystatin C>2), i.e. for CKD Stages 4 and 5, the Grubb prediction equation is less accurate. Based on our data, we suggest the equation GFR=50.52 C(-1.26) for this category of patients.
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