Methods: From all nephritic biopsies done between January 2000 and December 2004 in Mubarak Al Kabeer Hospital, instances of IgA kidney diseases were selected and their medical records every bit good as biopsy findings were reviewed.

Consequences: Eighty patients ( 9.2 % of all native kidney biopsies ) were diagnosed to hold IgA nephropathy. Sixty nine biopsies were included in the survey and eleven were excluded because of presence of any of the exclusion standards or losing clinical informations. Forty three ( 62.3 % ) instances were males, and 26 ( 37.7 ) instances were females. Fifty instances ( 72.5 % ) were below the age of 40 old ages. Average continuance of follow up was 3.6±1.3 old ages. The first presentation included nephrotic scope albuminuria ( 49.3 % ) , and nephritic damage ( 50.7 % ) . During the follow up period, 56 ( 81.2 % ) were stable or improved. Hass categorization of biopsies showed ; 36.2 % had Class I, 27.5 % had category II, 13.0 % had category III, 5.8 % had category IV, and 17.4 % had category V IgAN. Females had milder signifiers of the disease than males. Macroscopic haematuria and nephritic damage at presentation were seen more in patients with category IV and V. The presenting serum creatinine and uric acid were higher in those with Hass categories III to V. Deterioration of nephritic map during the follow up period was more important in presence of high blood pressure, nephritic damage and macroscopic haematuria at clip of biopsy.

Decision: The incidence of IgAN in Kuwait is approximately 9.2 % . Nephritic damage at presentation and macroscopic haematurias were seen in patients with more aggressive nephritic lesions and property to hapless result.

Cardinal words: Proteinuria, IgA nephropathy, nephritic Biopsy, Hass categorization

Introduction

IgA kidney disease ( IgAN ) was first described in

1968 by Berger and Hinglais. ( 1 ) It is now recognized as the most common primary glomerulonephritis worldwide. ( 2 ) It presents with haematurias and

frequently proteinuria. Although a moderate grade of albuminuria is common in patients with IgAN, nephrotic syndrome is considered uncommon in these patients. ( 3 ) The class of IgAN is variable, and 15 % -40 % of patients progress to end-stage nephritic disease over 10-20 old ages. ( 4 ) The pathogenesis of IgAN is complex and non wholly understood. Both environmental and familial factors have been found to be involved in the disease oncoming and patterned advance. ( 4,5 ) Humoral unsusceptibility is believed to play an of import function, characterized by the prevailing mesangial IgA1 deposition and associated secondary inflammatory response. ( 5 ) Curative attempts have been directed at either cut downing or forestalling antigen entry, and changing the unnatural immune response and its effects. However, the appropriate therapy for IgAN remains unsure and healing therapy is still non available. ( 6,7 )

The purpose of this survey was to reexamine instances of

IgAN in Mubarak Al kabeer Hospital- Kuwait between January 2000 and December 2004, and to analyze the spectrum of clinical presentation and histopathological findings

Method

All nephritic biopsies performed in Mubarak Al kabeer Hospital from January 2000 to December 2004 were retrospectively reviewed. Biopsies performed on grownup patients with IgAN were selected and reviewed. Patients were excluded from the survey if clinical or serologic grounds of Henoch Schonelin peliosis, collagen vascular diseases, liver cirrhosis, diabetes mellitus, or other kidney diseases were present. Kidney transplant instances were besides excluded from the survey. Clinical and research lab informations at presentation and during the follow up period and

the intervention given were obtained by careful retrospective survey of the infirmary records of each patient.

The histopathology glass slides were reviewed and the pathology studies were retrieved from the section of pathology computerized filing system. Each kidney biopsy was prepared by cutting paraffin blocks at 3 um subdivisions and staining 2 slides with peroidic acid schiff, 2 slides for Hematoxylin and Eosin, 1 slide for Jones Methenamine splinter and one slide for trichrome. Immunoperoxidase staining was besides performed routinely on all slides for IgG, IgA, IgM and C3. Antibodies were from Dako and titration was performed harmonizing to the cusps with the antibody phials.

Electron microscopy ( EM ) was non routinely done on all instances in the establishment, nevertheless, on selected instances EM was performed and the movies were retrieved and reviewed along with the EM study.

Statistical methods:

ISSN 1110-0834Numerical variables are expressed as Mean ± SD. The relation within and between the clinical and the histopathological variables were obtained utilizing ?2 trial or Fisher 's exact chance trial for categorical variables and nonparametric Mann Whitney U and Kruskal Wallis trials for uninterrupted variables. P & A ; lt ; 0.05 was considered as statistically important. Statistical analysis was performed utilizing SPSS for Windowss version 16 ( SPSS, Inc, Chicago, IL )

Consequence

A entire figure of 1575 nephritic biopsies were performed in the institute during the 5 old ages study period. Eight hundred 70 one biopsies were performed on native kidneys, and 704 were performed on transplanted kidneys. Eighty patients ( stand foring 9.2 % of the native kidney biopsies, 5.1 % of the entire biopsies ) were found to hold IgA nephropathy harmonizing to the biopsy consequences. Eleven patients were excluded from the survey because of losing informations or the presence of any of the exclusion standards. Sixty nine patients were enrolled in the survey. Forty three ( 62.3 % ) were males and 26 ( 37.7 % ) were females. The average age at presentation was 35.52±10.13 old ages. Fifty patients ( 72.5 % ) were below age of 40 old ages and 19 ( 27.5 % ) were ? 40 old ages. Average continuance of follow up was 3.6±1.3 old ages. Cases were presented by either microscopic ( 82.6 % ) or macroscopic haematurias ( 17.4 % ) .

Nephrotic scope albuminuria was seen in 34 ( 49.3 % ) instances while non-nephrotic albuminuria was detected in 35 ( 50.7 % ) instances. High blood pressure was detected in 35 ( 50.7 % ) of instances and nephritic damage was detected in 35 ( 50.7 % ) of instances. Fifty Six ( 81.2 % ) were stable or improved during the follow up period. Serum IgA, C3, and C4

degrees were all within the normal mention scope. Patient clinical and laboratory informations were mentioned in tabular array I.

Evaluation of nephritic biopsy slides was performed harmonizing to the Hass categorization of IgA nephropathy ( 8 ) showed ; 25 patients ( 36.2 % ) had Class I IgAN, 19 ( 27.5 % ) had category II IgAN, 9 ( 13.0 % ) had category III, 4 patient ( 5.8 % ) had category IV, and 12 patients ( 17.4 % ) had category V IgAN. ( table II ) ( fig 1, 2 )

Seven ( 10.4 % ) patients were treated with methyl Pediapred pulsation for crescentic lesions, 41 patients ( 59.4 % ) treated with unwritten steroids, 10 ( 14.5 % ) received mycophenolate mofetile or Imuran, 18 patients ( 26.1 % ) received cyclosporine, and 58 patients ( 84.1 % ) treated with angiotonin change overing enzyme inhibitors or angiotonin receptor blockers. Fish oil was given as an accessory therapy in 46 ( 66.7 % ) instances.

Females had milder histological signifier of the disease ( category I ) whereas males tended to hold more aggressive signifiers ( category IV and V ) ( P & A ; lt ; 0.05 ) . No relation was found between the Hass categorization and any of the age at presentation, high blood pressure, presence of hydrops or the degree of albuminuria ( P & A ; gt ; 0.05 ) . Macroscopic haematuria was seen more in category IV ( 75 % ) and category V ( 25 % ) than category I ( 8 % ) ( P & A ; lt ; 0.05 ) . Nephritic damage at presentation was seen more in patients with category IV ( 75 % ) and category V ( 91 % ) than category I ( 28 % ) ( P & A ; lt ; 0.001 ) . The showing serum creatinine and uric acid were higher in those with Hass categories III to V than category I and II ( P & A ; lt ; 0.001, & A ; lt ; 0.05 severally ) . ( table III )

Deterioration of nephritic map during the follow up period was more important in presence of high blood pressure, nephritic damage at clip of biopsy, and macroscopic haematuria ( P & A ; lt ; 0.05 ) whereas the showing degree of albuminuria, age, gender, and Hass categorization had a non important consequence on the impairment of kidney maps ( P & A ; gt ; 0.05 ) . The higher the showing serum creatinine the more the impairment of nephritic map during the follow up period ( P & A ; lt ; 0.05 ) . ( table IV )

Fig. 1: A instance of crescentic IgA kidney disease. Mesangial

enlargement with a cellular crescent. PAS x 400

Fig. 2: Immunoperoxidase staining shows a outstanding

Mesangial form. IgA immunoperoxidase x 400

Table I: Clinical and laboratory informations of patients holding IgA nephropathy ( n=69 )

Age in old ages ( mean±SD )

35.52±10.13

Gender ( male ) N ( % )

43 ( 62.3 )

Smoking N ( % )

17 ( 24.6 )

Hypertension N ( % )

35 ( 50.7 )

Hematuria N ( % )

Microscopic

Macroscopic

57 ( 82.6 )

12 ( 17.4 )

Proteinuria N ( % )

Nephrotic scope

Non- Nephrotic scope

34 ( 49.3 )

35 ( 50.7 )

Serum creatinine µmol/l ( mean±SD )

162.97±148.1

Creatinine clearance ml/min/1.73m2 ( average ± SD )

48.2±37.1

Nephritic damage N ( % )

35 ( 50.7 )

Serum albumen gm/l ( mean±SD )

31.33 ±7.08

Serum Cholesterol mmol/l ( mean±SD )

5.65±1.9

Serum Triglycerides mmol/l ( mean±SD )

1.96±1.1

Serum IgA degree gm/l ( mean±SD )

2.69±1.0

Serum C3 degree gm/l ( mean±SD )

1.04± 0.15

Serum C4 degree gm/l ( mean±SD )

0.94±0.12

Edema N ( % )

30 ( 43.5 )

Treatment given N ( % )

Methyl Pediapred pulsation

Angiotensin change overing enzyme inhibitors

Oral Steroids

Azathioprine

Cyclosporine

Fish oil

7 ( 10.1 )

58 ( 84.1 )

41 ( 59.4 )

10 ( 14.5 )

18 ( 26.1 )

46 ( 66.7 )

Duration of follow up ( mean±SD ) old ages

3.6±1.3

Prognosis N ( % )

Stable / Improved

Deterioration of nephritic maps

56 ( 81.2 )

13 ( 18.8 )

Table II: Histoathological spectrum of nephritic biopsy consequences harmonizing to Hass

categorization among IgA N patients ( n=69 )

Hass Classification

Number ( % )

Class I

25 ( 36.2 )

Class II

19 ( 27.5 )

Class III

9 ( 13.0 )

Class IV

4 ( 5.8 )

Class V

12 ( 17.4 )

Table Three: Relation between clinical presentation and Hass categorization ( n=69 )

Clinical and

research lab informations

Hass Classification

Trial of significance

P value

Class I

N ( % )

Class II

N ( % )

Class III

N ( % )

Class IV

N ( % )

Class V

N ( % )

Gender

Male

Female

12 ( 48 )

13 ( 52 )

10 ( 52.6 )

9 ( 47.4 )

7 ( 77.8 )

2 ( 22.2 )

3 ( 75 )

1 ( 25 )

11 ( 91.7 )

1 ( 8.3 )

& A ; lt ; 0.05*

Age at presentation

& A ; lt ; 40 old ages

& A ; gt ; 40 old ages

20 ( 80 )

5 ( 20 )

9 ( 47.4 )

10 ( 52.6 )

8 ( 88.9 )

1 ( 11.1 )

3 ( 75 )

1 ( 25 )

10 ( 88.3 )

2 ( 11.7 )

& A ; gt ; 0.05

High blood pressure

11 ( 44 )

9 ( 47 )

4 ( 44.4 )

3 ( 75 )

8 ( 66 )

& A ; gt ; 0.05

Edema

13 ( 52 )

6 ( 31.6 )

5 ( 55.6 )

2 ( 50 )

4 ( 33.3 )

& A ; gt ; 0.05

Nephrotic scope Proteinuria

12 ( 48 )

6 ( 31 )

5 ( 55.6 )

3 ( 75 )

8 ( 66.7 )

& A ; gt ; 0.05

Macroscopic haematuria

2 ( 8 )

4 ( 21 )

0 ( 0 % )

3 ( 75 )

3 ( 25 )

& A ; lt ; 0.01*

Nephritic damage

7 ( 28 )

8 ( 42.1 )

6 ( 16.7 )

3 ( 75 )

11 ( 91.7 )

& A ; lt ; 0.001*

Showing serum Creatinine µmol/l

84.4±31.7

171.3±179.6

203.2±198.7

288.5±84.5

278.5±140.1

& A ; lt ; 0.001*

Serum Uric acid mmol/l

312.6±71.8

381.4±171.3

428.2±20.3

459.5±188

412±143.9

& A ; lt ; 0.01*

Table Four: Factors finding deterioration of the kidney map during

the follow up Period ( n=69 )

Clinical and

research lab informations

Deterioration of kidney map

Trial of significance

P value

Yes

n ( % )

No

n ( % )

Gender

male

female

11 ( 25.6 )

2 ( 7.7 )

32 ( 74.4 )

24 ( 92.3 )

& A ; gt ; 0.05

Age

& A ; lt ; 40 old ages

& A ; gt ; 40 old ages

11 ( 22 )

2 ( 10.5 )

39 ( 78 )

17 ( 89.5 )

& A ; gt ; 0.05

High blood pressure

Yes

No

10 ( 28.6 )

3 ( 8.8 )

25 ( 71.4 )

31 ( 91.2 )

& A ; lt ; 0.05*

Hematurias

Microscopic

Macroscopic

8 ( 14 )

5 ( 41.7 )

49 ( 86 )

7 ( 58.3 )

& A ; lt ; 0.05*

Albuminurias

Non-Nephrotic scope

Nephrotic scope

5 ( 14.3 )

8 ( 23.5 )

30 ( 85.7 )

26 ( 76.5 )

& A ; gt ; 0.05

Nephritic damage at presentation

Yes

No

10 ( 28.6 )

3 ( 8.8 )

25 ( 71.4 )

31 ( 91.2 )

& A ; lt ; 0.05*

Edema

Yes

No

6 ( 20 )

7 ( 17.9 )

24 ( 80 )

32 ( 82 )

& A ; gt ; 0.05

Discussion

Many studies of glomerulonephritis associated with mesangial IgA sedimentations have been published since the original study of IgAN by Berger and Hinglais. The evident incidence of this upset

has varied in surveies from different states.

In France, ( 9 ) Spain, ( 10 ) Japan, ( 11 ) and Italy ( 12 ) the incidence has ranged from 11.7 to 43.3 % of nephritic biopsies. Much lower incidences have been reported in the United provinces, ( 13 ) England, ( 14 ) and Canada ( 15 ) with the incidence runing from 2.0 to 8.5 % in these states. Berger ( 16 ) suggested that the higher reported incidence of this disease in certain states compared to others may reflect the pattern of everyday one-year uranalysis in the states with

high incidence rates. To the best of our Knowledge this is the first survey from the Arab states showing the incidence of IgAN. We reported the incidence to be 9.2 % of native kidney biopsies

in Kuwait. Since the original description of IgAN,

a figure of surveies have attempted to correlate initial clinical and pathological findings with the subsequent class of the disease. The present survey was in conformity with the old surveies in demoing that females had milder pathologic

alterations whereas males were shown to hold

more aggressive signifiers. ( 17 ) There is a distinguishable geographical difference in the incidence of macroscopic haematuria in grownup patients. ( 18 ) In European states the reported incidence

exceeded 50 % , ( 19,20 ) whereas in Japan, the

incidence scope was from 15 to 31 % ( 21,22 ) This difference in distribution can be attributed to difference in the disease nature that could be linked to familial factors. ( 19 ) The predictive significance of macroscopic haematuria was controversial. In the present survey macroscopic haematuria was detected in 17.2 % of instances and found to be associated with aggressive histologic findings and correlatives with hapless forecast. This confirmed the consequences of the South West Pediatric Nephrology Study Group. ( 17 ) Furthermore, Bennet and Kinciad-Smith ( 23 ) reported that nephritic map became significantly worse in those with macroscopic haematurias, and emphasized the high incidence of crescent formation in these instances. However, Clarkson et Al. ( 24 ) demonstrated that nephritic map and lesions were significantly better in patients with macroscopic haematurias

than those without it. In our survey nephritic damage at presentation was seen more in patients with

category IV and category than category I. Correlation between more extended pathologic characteristics and terrible clinical manifestation were besides documented by Hass et Al. ( 25 )

The presenting serum uric acid correlated with

the diseased findings with higher degrees in

those with Hass categories III to V than category I and II. This confirmed the consequences of Myllimaki et Al. ( 26 ) who proved a strong correlativity between serum uric acid degree and badness of nephritic harm on biopsy.

The overall forecast of IgA N remains to be confirmed. In grownup surveies the incidence of

nephritic inadequacy varies from less than 10 % to 48 % in patients followed for more than 1 twelvemonth. ( 27 ) The present survey is in conformity with this

consequence as nephritic inadequacy was seen in 18.8 % of

instances. Bartosik et Al. ( 28 ) proved that the clinical parametric quantities, such as high blood pressure and badness of albuminuria appear to be stronger predictive indexs than histological findings. Furthermore,

Van Der Peer et Al. ( 29 ) found that those with

more high blood pressure, more albuminurias, and more pronounced histologic findings deteriorate their nephritic map more during follow up. Other survey showed that females and younger patients were found to hold a better forecast. ( 30 ) In the present work, impairment of nephritic map during the follow

up period was more important in presence of high blood pressure, nephritic damage, and macroscopic haematuria at clip of biopsy whereas, the showing degree of albuminuria, age, gender, and Hass categorization have a non important consequence on the impairment of kidney maps.

In decision, the incidence of IgAN in Kuwait

is 9.2 % . A multicenter survey should be conducted

to observe the exact incidence. About 18.8 % of

instances deteriorate their nephritic maps during the survey period but a longer follow up is needed.