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Renal Disease in Saudi Arabia: A Study of 147 Renal Biopsies

1984; King Faisal Specialist Hospital and Research Centre; Volume: 4; Issue: 4 Linguagem: Inglês

10.5144/0256-4947.1984.317

0975-4466

Wajeh Y. Qunibi, M. Badawi Al-Sibai, Saadi Taher, Mohammed Akhtar,

Renal Diseases and Glomerulopathies

Original ArticlesRenal Disease in Saudi Arabia: A Study of 147 Renal Biopsies Wajeh Y. Qunibi, MD, FACP M. Badawi Al-Sibai, MD Saadi Taher, and MB, ChB Mohammed AkhtarMD Wajeh Y. Qunibi Staff Nephrologist, Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia Search for more papers by this author , M. Badawi Al-Sibai Senior Resident, Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia Search for more papers by this author , Saadi Taher Staff Nephrologist, Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia Search for more papers by this author , and Mohammed Akhtar Staff Pathologist, Director of Electron Microscopy, Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia Search for more papers by this author Published Online::24 Apr 2019https://doi.org/10.5144/0256-4947.1984.317SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutABSTRACTABSTRACTIn an attempt to delineate the spectrum of renal disease in Saudi Arabia, as seen in kidney biopsies, a retrospective study of 147 renal biopsies performed on adult patients at King Faisal Specialist Hospital and Research Centre between 1975 and 1983 was conducted. Four groups of diseases were identified: Group I, which comprised primary and secondary glomerulopathies, represented the majority of cases (70.7%). Primary glomerulopathy accounted for half of all cases biopsied (51%). Group II consisted of diseases resulting from renal vascular injury (10.9%). Group HI were tubulointerstitial disease (7.5%) and Group IV were unclassifiable diseases reported as end-stage renal disease or chronic glomerulonephritis (10.2%). A relatively higher incidence of focal glomerulosclerosis and lower incidence of membranous glomerulonephritis was found than that seen in Western countries. There was also a much lower incidence of amyloidosis than in other studies from several Middle Eastern countries.INTRODUCTIONThe spectrum of renal disease in the Kingdom of Saudi Arabia is not known. The same is true for other Middle Eastern countries, although few papers have been published in this context.1–3 In this retrospective study an attempt is made to delineate, by studying kidney biopsies, the various renal diseases encountered at King Faisal Specialist Hospital in Saudi Arabia.MATERIALS AND METHODSThe medical records and renal pathology reports on all adult patients, excluding kidney transplant patients, who had a percutaneous renal biopsy at King Faisal Specialist Hospital and Research Centre were reviewed. Some of the early medical records were not available for review. From October 1975 until June 1983, 147 renal biopsies were performed on adult patients 16 years of age and over. Indications for renal biopsy were variable and included proteinuria with or without hematuria, unexplained renal insufficiency, and some systemic diseases such as lupus erythematosus with abnormal urinary findings. Biopsies were performed by three nephrologists. Tissue from one patient was inadequate for interpretation.Most renal biopsies were performed under ultrasonographic guidance and in some cases under fluoroscopy after intravenous injection of radiopaque contrast material. The latter method was used only if adequate renal tissue could not be obtained under ultrasonography. A Franklin-modified Vim-Silverman needle was used for biopsy. Two cores of renal tissue were usually obtained.The renal tissue obtained was submitted immediately to the pathologist who processed the specimens as follows:For light microscopic examination, the tissues were fixed in Bouin’s fixative or 10% buffered formalin solution and embedded in paraffin. Two-to three-micron sections were stained with hematoxylin and eosin, periodic-acid Schiff, trichrome, and methenamine silver stains. At least 20 sections were cut and examined in every case.For immunofluorescent microscopy, part of the biopsy was frozen, and 4-micron sections were cut. These were incubated with commercially available fluorescein-labeled antisera against IgG, IgM, IgA, C3, and fibrinogen using a direct technique. Renal tissues that were known positive and negative for these immunoglobulins were used as controls. These were examined with the fluorescence microscope using epifluorescence.For electron microscopy, tissue was fixed in 3% glutaraldehyde for at least 1 hour. Tissues were rinsed in Millonig’s phosphate buffer (pH7.2), postfixed in 1% osmium tetroxide, dehydrated in graded acetones, and embedded in Araldite Epon mixture. One-micron sections were stained with toluidine blue for orientation. Ultrathin sections were stained with uranyl acetate and lead citrate stain.RESULTSOf the 147 patients, 94 were men (63.9%) and 53 were women (36.1%) with a male-to-female ratio of 1.8:1.0. There were 129 Saudi patients (87.8%) and 18 non-Saudi patients, most of whom were other Arab nationals working in Saudi Arabia. The mean age of patients was 33 years with a range between 16 years and 72 years. Fig. 1 shows the frequency distribution of renal biopsies among the different age groups; 54 (36.7%) patients were between 20 and 29 years of age and 116 (78.9%) patients were between 20 and 49 years of age. The clinical features in the patients are listed in Table 1.Table 1. Clinical features in 147 patients with kidney biopsy*Fig. 1. Frequency distribution of renal biopsies among different age groups.Download FigureSome medical records were not available for review, especially those of the first few years. Of 115 patients with acceptable 24-hr urine collection for protein excretion, 60 (52.2%) had nephrotic-range proteinuria (i.e., > 3.5 gm/24 hr). Of the 60 patients, 39 (65%) had primary glomerulopathy, and 12 (20%) had glomerulopathy secondary to a systemic disease. Table 2 shows the histologic lesions en-countered in the nephrotic patients. Of the 129 patients who had their blood pressure recorded, 58 (45%) had hypertension, (blood pressure in excess of 145/95 mmHg). Abnormal renal function (serum creatinine > 1.5 mg/dl) was present in 49.1% of the patients and microhematuria (> 3 RBC per high-power field) was recorded in 65 out of 91 patients who had complete urinalysis (71.4%).Table 2. Histologic lesions encountered in nephrotic patientsThe final histologic diagnoses are listed in Table 3. A wide range of disease entities was encountered. These were grouped under four main headings:Table 3. Types of renal diseases found in 147 renal biopsies1. Group I—Glomerular diseasesA total of 104 patients (70.7%) had either primary glomerular disease or glomerular disease secondary to a systemic illness. In this group, 75 (72.1%) had a histologic diagnosis compatible with one of the primary glomerulopathies (Group IA) and 29 (27.9%) had lesions secondary to a systemic illness such as lupus erythematosus, vasculitis, amyloidosis, infection, or diabetes mellitus (Group IB).A. Twenty-three of the 75 cases (30.7%) of primary glomerulopathy had focal glomerulosclerosis. This category represented 15.8% of all cases biopsied. It was also the most common cause of nephrotic syndrome in this series, accounting for 23.3% of those with nephrotic-range proteinuria.The second most common form of glomerular disease in this series was mesangioproliferative glomerulonephritis, of which 19 cases were found, representing 25.3% of primary glomerulopathies and 13% of all cases biopsied. It was also the second most common cause of nephrotic syndrome, accounting for 13.3% of all cases with nephrotic-range proteinuria.Mesangioproliferative glomerulonephritis was distinguished from diffuse proliferative glomerulonephritis by the degree of proliferation, which was mild and limited to the mesangial region in the former. Furthermore, in mesangioproliferative glomerulonephritis, immunofluorescence microscopy was either negative or only showed small amounts of immunoglobulins, mostly IgM or IgG. The diffuse coarse granular pattern generally seen in diffuse proliferative glomerulonephritis was lacking. Ultrastructurally, only ill-defined deposits were seen in the mesangium.Membranous glomerulonephritis was found in six cases, representing 5.8% of the primary glomerulopathies and 4.1% of all cases in this study. This category represents 10% of all cases with nephrotic-range proteinuria and 15.4% of idiopathic nephrotic syndrome. All patients with membranous glomerulonephritis had nephrotic syndrome.Membroproliferative glomerulonephritis was the third commonest form of glomerular disease which was present in 13 cases, accounting for 17.3% of primary glomerulopathies and 9% of all cases biopsied. This entity was also the third commonest cause of nephrotic syndrome (11.7% of all cases with nephrotic syndrome) as 7 cases had nephrotic-range proteinuria. Table 3 shows the different categories in this group.B. Twenty-nine patients had glomerular disease secondary to a systemic illness, of which lupus nephritis was the most common. There were 13 cases of lupus nephritis, accounting for 44.8% of the secondary glomerular diseases and 8.9% of all cases in this study. Six patients with lupus nephritis had nephrotic syndrome, accounting for 10% of all cases with nephrotic-range proteinuria. It is important to point out that not all cases of lupus nephritis or diabetic nephrosclerosis were biopsied. Renal amyloidosis was present in four cases, representing 13.8% of secondary glomerular diseases, 3.8% of all glomerular diseases, and 2.7% of all cases in this study. It also accounted for 6.7% of all cases with nephrotic syndrome. All patients with renal amyloidosis had nephrotic-range proteinuria. Three of the patients had primary amyloidosis. The fourth case was secondary to rheumatoid arthritis. In only two of the cases was the disease suspected before biopsy.2. Group II—Renal diseases secondary to renal vascular injuryThere were 16 patients in this group. The majority (13 patients) had hypertensive arteriolonephro-sclerosis, representing 81.3% of this group and 8.8% of all biopsies in this study. Biopsies were made in these patients because of a combination of hypertension, renal insufficiency, and at times the presence of abnormal urine sediment. These patients usually had no past history significant for renal disease, and it was not known whether their hypertension was the primary event or was secondary to renal disease.Two patients had hypertension related to the third trimester of pregnancy. They were biopsied several weeks postpartum because of persistent hypertension and proteinuria. One patient, a primi-para, was found to have the classic lesions of preeclampsia. The other, a multipara, was found to have changes of chronic hypertension.One patient in this group had a history and physical signs of scleroderma. He had a renal biopsy because of rapid deterioration in renal function.3. Group III—Tubulointerstitial diseasesThere were 11 patients in this group. Five presented with renal failure of uncertain duration and on renal biopsy proved to have minor changes compatible with acute tubular necrosis. One of these patients also had granuloma and proved to have tuberculosis.Four patients had chronic interstitial nephritis most likely resulting from chronic pyelonephritis. Two patients had xanthogranulomatous pyelonephritis. Only one of these six patients had hypertension and none had microhematuria.4. Group IV—Unclassifiable renal diseasesIn this group there were 15 patients, representing 10,3% of all cases. In 10 cases, the pathologist thought that the changes were those of chronic glomerulonephritis; while in the other five the changes were so advanced that they were called end-stage renal disease (ESRD). Of the 15 patients, 12 were males and 3 females. Nephrotic-range proteinuria was present in 3 of the 10 cases with chronic glomerulonephritis but in none of the five cases with ESRD. One additional patient had inadequate renal biopsy tissue for interpretation.DISCUSSIONThe histologic pattern of renal disease in this series is listed in Table 3. A few differences exist between this study and those reported from the United States and Europe or from those reported in the Middle East.The most common histologic lesion encountered in this series was focal glomerulosclerosis (FGS), which was found in 15.8% of all biopsies. It also accounted for 30.7% of all patients with primary glomerular disease, for 23.3% of all with nephrotic syndrome, and for 35.9% with the idiopathic nephrotic syndromes. This makes FGS the most common cause of nephrotic syndrome in this series. Almost 70% of FGS cases presented with nephrotic-range proteinuria while the rest had non-nephrotic proteinuria with or without micro-hematuria; 45% of the patients had hypertension, and a quarter of patients had renal insufficiency at presentation. The incidence of FGS is slightly higher than the 10% reported from England4 and the United States.5Membranous glomerulonephritis (MGN) as a cause of nephrotic syndrome appears to be less common than that reported in Western countries. In this study, it represented 10% of all cases of nephrotic syndrome as compared with the 21% reported from Guy’s Hospital in England.4 It is also much less common than that reported from the United States where it accounted for over 50% of the cases with idiopathic nephrotic syndrome.5,6 In this study, MGN accounted for only 15.4% of all cases with idiopathic nephrotic syndrome. A similarly low incidence of MGN was reported in a study from Malaysia,7 in which no cases were found in adults of Indian origin. Also, low incidences of MGN were reported from Australia,8 where only two cases were encountered among 156 renal biopsies. Similar results were reported from Tunisia.9We have no explanation for the low incidence of MGN in this series. Although there is high incidence of HBsAg infections in Saudi Arabia, its presence does not seem to increase the incidence of MGN.A second interesting point is the low incidence of amyloidosis in this study as compared to that reported from Lebanon,1 Abu Dhabi,2 Turkey,3 and Jordan.10 This is despite the high prevalence of tuberculosis and other chronic infections in Saudi Arabia. Three of the cases of amyloidosis in the present study were primary amyloidoses, and only one was secondary to rheumatoid arthritis. However, another patient, not included in this study because no renal biopsy was done, had amyloidosis secondary to bronchiectasis. In that case the patient had nephrotic-range proteinuria, and rectal biopsy revealed amyloidosis. Table 4 shows the incidence of renal amyloidosis in various countries.Table 4. Incidence of amyloidosis in kidney biopsyThe reason for the low incidence of amyloidosis is not clear. Because referrals to King Faisal Specialist Hospital are made from all parts of Saudi Arabia, its patients are probably representative of various regions. The availability of specialized hospitals such as the Tuberculosis Centers and Fever Hospitals may reduce the number of patients with tuberculosis or chronic infections with proteinuria that would otherwise be referred elsewhere.Other patients with mild proteinuria may not have been referred. Still others may have end-stage renal disease and are being dialyzed elsewhere in the Kingdom. Some cases of amyloidosis could have been missed early on, before the availability of the electron microscope and the renal pathologist. However, this low incidence continues to be observed almost 6 years after these were acquired.In addition to the three primary and two secondary cases of renal amyloidosis mentioned above, only one other case has been seen at this hospital in a 6-year period, according to M. Kingston, MD and J. R. L. Froude, MD (written communication, 1983). This suggests that renal amyloidosis is not as common in this country as would be expected from the high prevalence of tuberculosis and chronic infections in Saudi Arabia.As a tertiary care center, King Faisal Specialist Hospital receives patients from all parts of the Kingdom. It is inevitable that this pattern of referral will affect the spectrum of renal disease seen, and it is not possible to determine whether or not the disease pattern seen in this study is truly representative of the spectrum of renal disease in Saudi Arabia.With this in mind, it can be speculated that the higher incidence of focal glomerulosclerosis in this study may be due to the fact that physicians tend to refer patients who fail to respond to a trial of steroid therapy. The same speculation cannot, however, explain the lower incidence of renal amyloidosis. The latter observation should be an interesting one to study.ARTICLE REFERENCES:1. 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Zollinger HU, Mihatsch MJ: Renal Pathology In Biopsy: Light, Electron and Immunofluorescent Microscopy and Clinical Aspects. Berlin, Springer-Verlag, 1977, pp 382–91. Google Scholar13. Bergertranel AF, Bucht H: Renal amyloidosis. In: Becker EL (ed.) Structural Basis of Renal Disease. New York, Hoeber, 1968, pp 505–17. Google Scholar14. Chugh KS, Singhal PC, Sakhuja V, et al.: "Pattern of renal amyloidosis in Indian patients" . Postgrad Med J 57:31–51981. Google Scholar Previous article Next article FiguresReferencesRelatedDetails Volume 4, Issue 4October 1984 Metrics History Published online24 April 2019 InformationCopyright © 1984, Annals of Saudi MedicinePDF download