Pattern of Renal Disease in the Elderly Biopsy Based Data from a Single Center in Kurdistan Region-Iraq: A 7-Year Retrospective Study

Kawa Hussein Amin^*

^*Correspondence: Kawa Hussein Amin, Department of Medicine, College of Medicine, University of Sulaimani, Iraq, Email:

Author info »

Introduction

Aging and old age are among the most significant challenges facing medicine this century. Modern medicine and healthier lifestyles have increased the likelihood that younger adults will now achieve old age [1]. This increase in life expectancy is associated with more chronic and acute disease in the elderly. As there is physiologic decline in the kidney function with aging, the elderly are more vulnerable to chronic progressive kidney disease as well as any superimposed acute injury to the kidneys [2]. Previously renal biopsies of the elderly were not performed routinely. However in recent studies renal biopsy is considered to be a safe procedure even in the elderly and yields valuable information which can help decide the patient management and prognosis [3]. Renal biopsy remains a valuable clinical tool and generally required to establish the type of glomerular disease, reflect the level of disease activity and to guide treatment decision. It is able to provide a tissue diagnosis in more than 95% of patients, with a life-threatening complication rate of less than 0.1% [4]. It is mandatory to recognize the spectrum of renal disease in the elderly in order to understand the etiology as well as factors of disease progression to end stage renal disease [5].

Studies about the patterns and prevalence of renal diseases in Kurdistan region-Iraq are extremely rare and exact incidence of renal disease in the elderly is not known, because of very limited information available on that age group and overall spectrum of clinical renal disease in the elderly from our country. Therefore, this study is conducted to analyse the relative frequencies of kidney diseases in the aged population, and to better understand the natural history of renal diseases in this region. The study was performed based on renal biopsies obtained from the histopathology center in Sulaimani Governorate-Iraq. The results are compared with similar reports from other countries.

Materials and Methods

This is a retrospective study with approve of Shorsh hospital research committee of renal biopsies performed over a period of 7 years from January 2010 to December 2016, at Shorsh hospital in Sulaimani Governorate which provides the renal histopathological service for the entire population of North-Iraq (Kurdistan Region) in a single center. Collectively a total number of 2779 renal biopsies were performed of which 191 cases were excluded from the study because of either having insufficient samples or not having proper clinical data, and another 674 cases were excluded since they were taken from transplanted subjects.

In total, 1914 renal biopsies remained of which 135 cases were obtained from elderly patients. A retrospective analysis was conducted with the (≥ 60 years) age group. Individuals aged 60 years or above (≥ 60 years) were arbitrarily considered elderly. There were 92 males and 43 females with age ranging from 60 years to 83 years. The indications for renal biopsy included (proteinuria, unexplained microscopic or macroscopic hematuria, systemic disease with evidence of renal involvement and unexplained renal impairment).

The following data were recorded for each patient: name, age, sex, source of referral, indication for renal biopsy, histopathological diagnosis and laboratory investigations such as serum creatinine, 24-hour urinary protein, urine microscopy, virology (HBs-Ag, anti-HCV, HIV) and serology (anti-dsDNA antibody, antinuclear antibody ANA, C3, C4). All samples were obtained by percutaneous method using a true-cut needle under ultrasound guidance and a (16 G × 16 cm) size instrument was used. Specimens obtained were prepared as per the standard protocol and examined by the same group of pathologists and technicians of our hospital. Analysis included Light microscopy (LM) and immunofluorescence (IF). For LM, Sections were made from formalin fixed paraffin embedded tissue and three sections were stained with Hematoxylin and Eosin, one with periodic acid Schiff, and one with Masson’s trichrome. Special stains were used when warranted.

IF (Immunofluorescence microscopy) panel included staining for IgG, IgM, IgA, C3, C1q, and kappa and lambda light chains. During 2010 IF analysis was not available, but afterwards it was performed in majority of the biopsies.

Histological categories were classified as follows:

• Primary glomerulonephritis (PGN): Focal segmental glomerulosclerosis (FSGS), Membranous nephropathy (MN), Minimal change disease (MCD), Membrano-proliferative glomerulonephritis (MPGN), Post-infectious glomerulonephritis (PIGN), Immunoglobulin A nephropathy (IgAN), Crescentic glomerulonephritis (CresGN) and Mesangioproliferative glomerulonephritis (MesPGN).

• Secondary glomerulonephritis (SGN): Lupus nephritis (LN), Diabetic nephropathy (DN), Hypertensive nephrosclerosis (Hypertensive NS), and Amyloidosis (AM).

• Tubulo-interstitial nephropathies (TIN): Tubulointerstitial nephritis either acute TIN or chronic TIN and Acute tubular necrosis (ATN).

• Miscellaneous: (Nephrocalcinosis, Thrombotic microangiopathy, Cast nephropathy, Burkitt lymphoma, Pyelonephritis and Cystic kidney).

• Normal kidney biopsy.

Data analysis

Collected data were treated statistically using Statistical Package for the Social Sciences (SPSS) version 21 for the data analysis and Microsoft Excel 2010 was used for data entry as well as for designing of the graphs. Data are expressed as means ± standard deviations. Descriptive statistics were generated on all variable, chi square tests were used to investigate the associations present. p-value less than 0.05 was considered significant.

Results

One hundred and thirty five renal biopsies of patients aged 60 years or above were retrospectively analysed after exclusion of the renal biopsies from younger age groups, renal graft and those with insufficient records. Their mean age was 67.2 ± 6.3 years, ranged from sixty years to eighty three years. The male sex prevailed 92 cases (68.1%) with females comprising 43 cases (31.9%) of the study.

Higher number of biopsies was taken during the last four years and variation was observed in each type of renal disease according to time periods. Immuno-fluorescence test was not available in 2010 then afterwards it was performed for most of the biopsies. The total number of biopsies performed per-year together with IF analysis performance rate is shown in Figure 1. Also the distribution of various types of renal disease in each year is shown in Table 1.

Figure 1. The total number of biopsies performed per-year with IF analysis performance rate.

Table 1: The distribution of different types of renal disease in each year

The most frequent clinical presentations prior to renal biopsy or indications were; proteinuria (69.6%), renal impairment (55.6%), hypertension (34.8%), hematuria (21.5%), and Diabetes (10.4%). As demonstrated in Table 2. The most common histopathological findings in elderly are shown in Figure 2. Glomerular disease was the most frequent diagnosis (82.3%) either PGN (51.9%) or SGD (30.4%) followed by Miscellaneous (9.6%) including (Nephrocalcinosis, Thrombotic microangiopathy, Cast nephropathy, Burkitt lymphoma, Pyelonephritis and Cystic kidney) and TIN (6.7%).

Table 2: Clinical presentation of patients prior to renal biopsy

Figure 2. The overall frequencies of different renal diseases in native renal biopsies in the elderly.

There were 70 cases of PGN comprising (51.9%) of renal diseases. FSGS was the most common type of PGN observed in 28 cases (40.0%), followed by MN 18 cases (25.7%) and Cres GN 9 cases (12.9%). MCD was found in 6 cases (8.6%), MPGN in 5 cases (7.1%), IgA N in 3 cases (4.3%) and PIGN in 1 case (1.4%). There were 41 cases of SGN constituting (30.4%) of the total biopsies, Hypertensive NS was the most frequently diagnosed disease 28 cases (68.3%) of SGN, followed by the second most common diagnosis AM 10 cases (24.4%). DN was found in 2 cases (4.9%) and LN was encountered in minority of patients 1 case (2.4%).

Discussion

The current study provides the latest comprehensive information about the demographics, clinical presentations and pattern of kidney diseases in elderly patients from a 7-year period in a single center in Kurdistan region-Iraq. To the best of our knowledge, this is the largest renal biopsy series and the first to analyze patients aged ≥ 60 years in Iraq. Clinico-pathological data of 1914 patients who underwent renal biopsy between the years (2010-2016) were analyzed, in which 135 cases were elderly.

In our study population the male sex prevailed 92 cases (68.1%) and 43 cases (31.9%) were female, this’s similar to other studies assessing the same age group in the United Kingdom and Italy [6,7]. This finding suggests that males are more susceptible to kidney diseases and another notable outcome identified was the male sex predominance for all histopathological categories of biopsy proven glomerulonephritis with the exception of Lupus nephritis, in which females were more frequently affected.

The recent study identified proteinuria as the most frequent clinical manifestation indicating renal biopsy in (69.6%) of all cases, followed by renal impairment (55.6%), hypertension (34.8%), hematuria (21.5%), and Diabetes (10.4%). This is consistent with other reports published in Poland, Spain and the United States [8-10]. On the other hand studies from Spain and the United States reported acute kidney injury as the commonest presentation [11,12].

Among the biopsy proven renal disease in the elderly, glomerular disease was the most frequent finding being diagnosed in (82.3%) of all cases. Primary glomerulonephritis was the most common diagnosis (51.9%) followed by Secondary glomerulonephritis (30.4%), Miscellaneous (9.6%) including (Nephrocalcinosis, Thrombotic microangiopathy, Cast nephropathy, Burkitt lymphoma, Pyelonephritis and Cystic kidney) and Tubulointerstitial nephropathies (6.7%). which is similar to studies performed in China and India [13,14].

In elderly patients, Membranous nephropathy is known to be the most common histological pattern according to studies conducted in India, Korea, Ireland, Japan, India, Brazil and Saudi Arabia [15-21]. In our study, Focalsegmental glomerulosclerosis (40.0%) and Membranous nephropathy (25.7%) were first and second most common type of primary glomerulonephritis; this is concordant with the outcome in a study from Japan [22]. There are some discrepancies in the frequencies and spectrums of glomerular diseases in different countries and regions. In this regards, the primacy of Focalsegmental glomerulosclerosis is noteworthy since Focalsegmental glomerulosclerosis is a heterogeneous lesion and its incidence is on the rise throughout the world, both in adults and children.

Hypertensive nephrosclerosis was the most common histological pattern among the Secondary glomerulonephritis, a finding justified by the high prevalence of arterial hypertension in that age group, which can reach up to (68.3%) of the Secondary glomerular nephropathies, which’s compatible with a report in Brazil [23]. Whereas a study from China reported Diabetes nephritis as the most common secondary glomerulonephritis [24]. Other studies from Turkey and India have shown Amyloidosis to be the commonest [25,26]. A research examined Records of all elderly patients (≥ 60 years) who had undergone kidney biopsy in the nephrology department. Their clinical details and laboratory investigations at the time of biopsy were noted. Details of kidney biopsy were recorded from their biopsy reports. Like our paper, they showed spectrum of biopsy-proven kidney disease in the elderly Indians seen in tertiary care hospital varies from the younger population. Kidney biopsy provides useful information with therapeutic and prognostic implications in these patients. The percentage of elderly patients among the total biopsied population is low in India, and these patients present late with renal dysfunction. Prospective studies are needed to assess the outcome of the commonly seen kidney diseases in elderly patients [27].

Conclusion

In conclusion, renal biopsy is a useful modality to diagnose kidney disease in the elderly population, providing us with important diagnostic information that can guide treatment and planning appropriate management. In our study, Primary glomerular disease constituted majority of the biopsies followed by Secondary glomerular disease. Among the Primary glomerulonephritis Focal-segmental glomerulosclerosis and Membranous nephropathy were the most common findings, and regarding the Secondary Glomerular diseases Hypertensive nephrosclerosis was the commonest followed by Amyloidosis.

Limitations

• We were unable to analyze the data for the period before 2010 due to unavailability of a Histopathological center for renal biopsy in Kurdistan Region.

• After establishment of the center in Sulaimani Governorate, immunofluorescence test was not present for the first year (2010).

• Another shortcoming of our study was unavailability of Electron microscopy, which would have helped in better and more precise diagnosis.

• Inadequate clinical data was another factor.

Acknowledgment

We thank all the participating staff in Shorsh General Hospital-Sulaimani Governorate for performing the biopsies and collecting the reports.

Conflict of Interest

The authors declare that there is no conflict of interest regarding the publication of this article.

References

1. Kasper DL, Fauci A, Hauser S, et al. Harrison's Manual of Medicine, 19e. McGraw-Hill Education, USA, 2015.
2. Bagchi S, Mittal P, Singh G, et al. Pattern of biopsy-proven kidney disease in the elderly in a tertiary care hospital in India: A clinic-pathological study. Int Urol Nephrol 2016; 48:553-60.
3. Kohli HS, Jairam A, Bhat A, et al. Safety of kidney biopsy in elderly: A prospective study. Int Urol Nephrol 2006; 38:815-20.
4. Johnson RJ, Feehally J, Floege J. Comprehensive clinical nephrology, (5th Edn) Elsevier Health Sciences, UK.  2015.
5. Zhu P, Fu-de Zhou MH. The renal histopathology spectrum of elderly patients with kidney diseases: a study of 430 patients in a single Chinese center. Medicine 2014; 93.
6. Davison AM, Johnston PA. Glomerulonephritis in the elderly. Nephrol Dial Transplant 1996; 11:34-7.
7. Schena FP. Survey of the Italian registry of renal biopsies. Frequency of the renal diseases for 7 consecutive years. The Italian group of renal immunopathology. Nephrol Dial Transplant 1997.
8. Ptasinska PA, Materkowska DD, Bartczak A. Kidney disease in the elderly: Biopsy based data from 14 renal centers in Poland. BMC Nephrology 17.
9. Rivera F, Gomez LJM, Garcia PR. Clinicopathologic correlations of renal pathology in Spain. Kidney Int 2004; 66:898-904.
10. Haas M, Spargo BH, Wit EJ, et al. Etiologies and outcome of acute renal insufficiency in older adults: A renal biopsy study of 259 cases. Am J Kidney Dis 2000; 35:433-47.
11. Verde E, Quiroga B, Rivera F, et al. Renal biopsy in very elderly patients: Data from the Spanish registry of glomerulonephritis. Am J Nephrol 2012; 35:230-7.
12. Moutzouris DA, Herlitz L, Appel GB, et al. Renal biopsy in the very elderly. Clin J Am Soc Nephrol 2009; 4:1073-82.
13. Chen Y, Li P, Cui C, et al. Biopsy-proven kidney diseases in the elderly: Clinical characteristics, renal histopathological spectrum and prognostic factors. J Int Med Res 2016; 44:1092-102.
14. Lingaraju U, Varma SS, Satishkumar MM. Spectrum of glomerular diseases–clinic-pathologic observations from a state run tertiary care centre. Int J Res Med Sci 2015; 3:2004-13.
15. Prakash J, Saxena RK, Sharma OP. Spectrum of renal diseases in the elderly: Single centre experience from a developing country. Int Urol Nephrol 2001.
16. Shin JH, Pyo HJ, Kwon YJ. Renal biopsy in elderly patients: Clinicopathological correlation in 117 Korean patients. Clin Nephrol 2001; 56:19-26.
17. Hanko JB, Mullan RN, O´Rourke DM, et al. The changing pattern of adult primary glomerular disease. Nephrol Dial Transplant 2009; 24:3050-4.
18. Komatsuda A, Nakamoto Y, Imai H. Kidney diseases among the elderly-A clinicopathological analysis of 247 elderly patients. Int Med 1993; 32:377-81.
19. Prakash J, Singh A, Saxena R. Glomerular diseases in the elderly in India. Int Urol Nephrol 2003; 35:283-8.
20. Oliveira DC, Costa R, Vieira NO. Renal diseases in the elderly underwent to percutaneous biopsy of native kidneys. J Bras Nefrol 2010; 32:379-85.
21. Jalalah SM. Patterns of primary glomerular diseases among adults in the western region of Saudi Arabia. Saudi J Kidney Dis Transpl 2009; 20:295-9.
22. Uezono S, Hara S, Sato Y, et al. Renal biopsy in elderly patients: A clinicopathological analysis. Renal Failure 2006; 28:549-55.
23. Carmo PAVD, Kirsztajn GM, Carmo WBD. Histopathological findings in elderly patients. J Bras Nefrol 2010; 32:286-91.
24. Jin B, Zeng C, Ge Y, et al. The spectrum of biopsy-proven kidney diseases in elderly Chinese patients. Nephrol Dial Transplant 2014; 29:2251-59.
25. Harmankaya O, Okuturlar Y, Kocoglu H. Renal biopsy in the elderly: A single-center experience. Int Urol Nephrol 2015; 47:1397-401.
26. Gupta P, Rana DS. Importance of renal biopsy in patients aged 60 years and older: Experience from a tertiary care hospital. Saudi J Kidney Dis Transpl 2018; 29:140-4.
27. Bagchi S, Mittal P, Singh G, et al. Pattern of biopsy-proven kidney disease in the elderly in a tertiary care hospital in India: A clinicopathological study. Int Urol Nephrol 2016; 48:553-60.