| Abstract|| |
Glomerulonephritis (GN) is a major cause of chronic renal failure (CRF). To evaluate the trends and outcome with modern improved treatment strategies, we retrospectively reviewed the clinical records of 120 patients with biopsy proven primary GN at our center from January 1990 to June 2001. All the biopsy specimens were subjected to light, electron and immunofluorescent microscopy. The recorded clinical parameters included the presenting symptoms, blood pressure readings, complete blood count, urinalysis, 24-hr urinary protein excretion, creatinine clearance besides rendered therapy and the outcome. Focal segmental glomerulosclerosis was the most common GN and accounted for 56 (47.6%) cases. The frequency of other GN cases in our study included IgA GN in 21 (17.5%) patients, membranous GN in 20 (16.7%), minimal change disease (MCD) in 13 (10.8%), membranoproliferative GN in 4 (3.3%), post infection in 4 (3.3%) and rapidly progressive glomerulonephritis (RPGN) in 2 (1.7%). The type of nephropathy had great influence on outcome and response to therapy. The deterioration of patients with FSGS was the fastest of the glomerulopathies, and nine (16.1%) patients developed end-stage renal failure (ESRD). MCD and post infection GN had the best outcome. Corticosteroids alone along with supportive medication conferred good results in MCD, while combined therapies of mycophenolate mofetil (MMF) and/or cyclophosphamide with corticosteroids provided better outcomes in the rest of the GN. RPGN responded well to the cyclophosphamide and the patients did not develop ESRD. Hyperuricemia, high serum creatinine and hypertension predicted worse outcomes. The control of blood pressure and glucose, and treatment of hyperuricemia and hypoalbuminemia had salutary effect on the outcome. We conclude that due to the better delivered care the outcome of primary GN has improved over the years. However, FSGS is still the most frequently encountered primary GN and has the worst outcome. In the present study, combined therapies with corticosteroids and cytotoxic drugs and supportive therapy were associated with better outcome.
Keywords: Glomerulonephritis, Primary, Therapy, End-stage, Renal, Failure.
|How to cite this article:|
Al Wakeel JS, Mitwalli AH, Tarif N, Alam AA, Hammad D, Abu-Aisha H, Memon N, Sulimani F, Askar A, Qudsi A. Spectrum and Outcome of Primary Glomerulonephritis. Saudi J Kidney Dis Transpl 2004;15:440-6
|How to cite this URL:|
Al Wakeel JS, Mitwalli AH, Tarif N, Alam AA, Hammad D, Abu-Aisha H, Memon N, Sulimani F, Askar A, Qudsi A. Spectrum and Outcome of Primary Glomerulonephritis. Saudi J Kidney Dis Transpl [serial online] 2004 [cited 2019 Jul 18];15:440-6. Available from: http://www.sjkdt.org/text.asp?2004/15/4/440/32875
| Introduction|| |
Glomerulonephritis (GN) is a major cause of chronic renal failure (CRF) and end-stage renal disease (ESRD)  that requires renal replacement therapy, which has great financial burden on any health budget. Therefore, the trends of GN, their racial and geographical variations, and factors contributing to progressive functional deterioration of the renal function must be studied in order to develop better strategies of management of these lesions.
Recently early detection of GN and/or advanced treatment with strict monitoring of blood pressure, diabetes and proteinuria along with supportive medication such as erythropoietin for anemia, albumin and antioxidant vitamins have changed the outcome of patients with GN.
We aim in this study to describe our experiences with primary GN including their presentation, prevalence, trends, course, treatment provided and outcome.
| Materials and Methods|| |
We retrospectively reviewed the medical records of 120 patients with biopsy proven primary GN at our center from January 1990 to June 2001. All the biopsy specimens were subjected to light, electron and immunofluorescent microscopy. The studied clinical variables included findings such as proteinuria, hematuria, hypertension, edema or infection. The laboratory investigations included serum creatinine, blood urea, 24-hr urinary protein, creatinine clearance, complete urinalysis, urine culture, serum uric acid, triglyceride and cholesterol, complete blood count, liver function tests and fasting blood sugar. All lab values were recorded at first follow up and 6 monthly thereafter till last follow up.
Therapy intended for the primary GN such as corticosteroids and cytotoxic agents, antihypertensives and supportive medications such as erythropoietin, albumin, calcium carbonate, antioxidants and vitamins were reviewed. The antihypertensives included beta-blockers in 46 (38.3%) angiotensin converting enzyme inhibitors (ACEI) in 62 (51.66%), Calcium channel blockers (CCB) in 29 (24.1%) and diuretics in 41 (34%).
Stat pack gold statistical package was used for analysis of the collected data. Values are presented as mean ± Standard error (SE). Regression analysis was used to see the effect of baseline covariates like age, sex, serum creatinine, 24-hr urinary protein, uric acid, hypertension and diabetes on the progression of disease. Student "t" test was done to compare the values and level of significance that was set as P<0.05. Furthermore, the life table method was used to obtain the hazard function for the rates of doubling of baseline serum creatinine concentrations in relation to duration of follow-up BmDP statistical package was used for this analysis.
| Results|| |
The mean age of the patients at the time of presentation was 34.6 ± 13.5 years and 68 (56.6%) were males. The mean follow-up period of the patients was 7 ± 0.9 years. Focal segmental glomerulosclerosis was the most common GN and accounted for 56 (47.6%) cases. The frequency of other GN cases in our study included IgA GN in 21 (17.5%) patients, membranous GN in 20 (16.7%), minimal change disease (MCD) in 13 (10.8%), membranoproliferative GN in 4 (3.3%), post infection in 4 (3.3%) and rapidly progressive glomerulonephritis (RPGN) in 2 (1.7%).
Heavy proteinuria was found in 25 (20.8%) patients, hematuria in 45 (37.5%), impairment of renal function in 50 (41.6%), edema in 34 (28.33%) and infection in 4 (3.3%). The mean systolic blood pressure (BP) was 133 ± 18 mmHg and diastolic BP was 85 ± 3.0 mmHg.
The baseline laboratory values were: serum creatinine 139 ± 103, proteinuria 2.56 ± 2.15, creatinine clearance 68.8 ± 34.9 µmol/L, serum albumin 35 ± 10 gm/L, urea 10 ± 9.1 mmol/L, uric acid 393.2 ± 121.31 mmol/L, hemoglobin 130 ± 26 gm/L HCT, 40 ± 25%, platelets 277 ± 87 x 10 3 /µL, Na + 138 ± 1.5 mmol/L, K + 5.7 ± 0.3, triglycerides 3.5 ± 1.1 mmol/L, cholesterol 5.9 ±1.4 mmol/L. [Table - 1] shows the clinical and laboratory characteristics in patients in each GN found in our study.
[Table - 2] shows that 94 (78.3 %) patients received corticosteroids alone, and 20 (16.7%) received steroids along with cytotoxic agents including two patients who received MMF along with steroids, the treatment choice and outcome of the treated patients in our study.
[Table - 3] shows that 37 (30.8%) patients deteriorated, while 83 (69.2%) patients remained stable or improved; 29 (24.1%) patients improved to normal (ie. the levels of serum creatinine, 24-hr urinary protein, creatinine clearance, uric acid and serum albumin and cholesterol as well as blood pressure).
[Table - 4] shows that 33 (27.5%) patients had doubling of serum creatinine at last followup. Nine FSGS patients, two IgA and one mesangioproliferative nephropathy patients developed ESRD. A life table analysis showed fastest rate of doubling of baseline serum creatinine in FSGS patients [Figure - 1]. [Table - 5] shows the serum creatinine level during the follow-up period during the first and last visits.
BP was well controlled at last follow-up compared to baseline that there was a 9.1% relative risk reduction in systolic BP and 30% relative risk reduction in diastolic BP . A similar improvement in cholesterol 5.8 ± 0.7 vs 5.1 ± 0.8 mmol/L was observed due to the lipid lowering medication in these patients; 17 patients had serum cholesterol above 6 mmol/L at baseline (normal < 5.2 mmol/L) and decreased to 3 patients at last follow- up. Triglycerides plasma level normalized from 3.5 ± 1.1 at first follow up to 1.78 ± 0.327 mmol/L at last follow- up in the same number of patients as cholesterol.
There were 43 (35.8%) patients who had hyperuricemia at baseline; 9 patients had uric acid between 350 - 400 mmol/L, 17 (14.2%) patients had uric acid levels between 401- 450 mmol/L and another 17 (14.2%) patients had uric acid levels between 451-550 mmol/L. There was a good correlation between baseline uric acid and level of renal dysfunction; r = 0.6, P < 0.0001.
Remarkably, all patients with ESRD had high uric acid initially above 450 mmol/L (normal upper limit for uric acid is 325 mmol/L). In these patients diastolic blood pressure (r = 0.6 p = 0.0001), systolic blood pressure (r = 0.3, p = 0.0017), uric acid (r = 0.7, p = 0.00001) serum creatinine (r = 0.7, p = 0.0001) had stronger correlation with progression to ESRD than other parameters such as hematuria (r = 0.08, p = 0.6).
Among covariates, after serum creatinine baseline serum uric acid more than 450 mmol/L and baseline BP had statistically marked influence on progression to CRF and ESRD irrespective of underlying renal disease r = 0.67 and r = 0.63 respectively.
| Discussion|| |
In the present study FSGS was the predominant form of primary GN. Our findings are close to the previously published reports from Saudi Arabia as Quinibi et al  in 1984 reported the prevalence of FSGS as 22.1%, while Jorgenson et al  in 1985 found it to be 7.1%. In 1990, Huraib et al  found FSGS to be 11.4%, while Akhtar et al  reported it FSGS to be 40.8% in 1996 and 34.6% from to be 34.9% and Mitwalli et al , found the central province of Riyadh, Saudi Arabia in 1999. An increasing trend is noted for FSGS in Kingdom of Saudi Arabia. Similar increasing incidence is found to be in some other parts of the world also. , Piero et al have found a 10 fold increase in the incidence of FSGS over 20 years period in Europe while Braden et al  in 2000 reported a 22.6% increase in the incidence of FSGS over four years in U.S.A. In the present study FSGS was the leading cause of Nephrotic Syndrome and presented with nephrotic range of proteinuria, hypertension and hematuria. Deterioration of renal function was fastest and 20 (21.2%) had doubling of serum creatinine within 3.9 + 0.8602 years and 9 (16.1%) patients went into ESRD.
In our study, the patients with FSGS progressed to ESRD more than other primary GN. However, the total number of patients with renal failure was less in the present study as compared to past studies ,, Furthermore, the patients in the present study who progressed to CRF had high baseline uric acid and serum creatinine at the time of presentation. A similar relationship of high serum creatinine with worse outcome was reported by previous studies. 
In our study, IgA and mesangioproliferative GN accounted for similar percentage (17%) reported before from Saudi Arabia but smaller percentage of the primary GN in comparison to the far eastern countries like China, Hong Kong and Taiwan, where IgA is the commonest and predominant GN accounting for 50% of total number of the encountered cases. , However, the outcome of this GN was marginally less favorable than the past experience from Saudi Arabia, where 50% of patients developed CRF over 20 years compared to 42% over nine years in our study. 
In the present study, the minimal change disease had a favorable outcome, while the patients with post infection GN were quite less in number and all the patients recovered completely with no immunosuppressant. The patients with RPGN in the present study responded well to the steroids and cytotoxic medication and their condition improved and none of them developed ESRD.
Due to the supportive medication in the present study, there was a great overall decrease in the 24-hr urinary protein excretion, with improvement of serum albumin and hemoglobin. Furthermore, we could reduce the level of serum uric acid, triglycerides and cholesterol, and control of BP.
We conclude that due to the better delivered care the outcome of primary GN has improved over the years. However, FSGS is still the most frequently encountered primary GN and has the worst outcome. In the present study, combined therapies of corticosteroids and cytotoxic drugs besides supportive management were associated with better outcome.
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Jamal S Al Wakeel
Department of Medicine (38), King Khalid University Hospital, P.O. Box 2925, Riyadh, 11461
[Figure - 1]
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5]