ABSTRACT
Kidney disease is common in older adults due to age-related structural and functional changes in the kidneys, higher rates of chronic disease, and increased drug use. As societies age, there is a rise in the prevalence of renal disease and the number of kidney biopsies being performed in older patients. This study aimed to investigate renal biopsy indications, complications, pathology results, and subsequent treatment among older adults in Turkey.
We retrospectively analyzed data from patients aged 65 and over who underwent renal biopsy in a university nephrology department between 2004 and 2023. The patients’ demographic information, chronic comorbidities, biopsy indications, pre-biopsy laboratory values, post-biopsy complications, pathology results, and post-biopsy treatments were obtained by reviewing their medical records and biopsy reports.
A total of 66 patients were included in the study. The median age was 73.0 years (IQR: 68.8-79.0 years) and 66.7% of the patients were men. The most common comorbidities were hypertension (83.3%), diabetes mellitus (24.3%), coronary artery disease (22.7%), and chronic kidney disease (21.2%). The most common indication for renal biopsy was nephrotic-range proteinuria (56.1%), followed by acute kidney injury (24.2%). When the pathology results were examined, primary glomerulonephritis (62.1%) was the most common result, followed by secondary glomerulonephritis (21.2%) and tubulointerstitial nephritis (12.1%). The most common histopathological diagnoses in primary glomerulonephritis were membranous glomerulonephritis (39.4%) and focal segmental glomerulosclerosis (12.1%), while those in secondary glomerulonephritis were secondary amyloidosis (9.1%) and lupus nephritis (4.5%). After biopsy, 54.5% of the patients received immunosuppressive therapy and 34.8% received renal replacement therapy. No post-biopsy complications were observed.
Although the most common indication for kidney biopsy in older adults is nephrotic-range proteinuria. Kidney biopsy is the gold standard method for the diagnosis of renal parenchymal diseases and is a safe procedure in older patients, with low complication rates. Kidney biopsy should not be avoided in geriatric patients if deemed clinically necessary.
INTRODUCTION
Kidney disease is a common clinical problem in the elderly and is associated with increased mortality and morbidity. The prevalence of many kidney diseases, especially chronic kidney disease (CKD), increases in the elderly. This is mainly attributed to the increasing prevalence of traditional risk factors for kidney diseases, such as diabetes mellitus (DM), hypertension (HT) and cardiovascular diseases, and changes in the genitourinary system with aging1, 2. Various anatomical and functional changes occur in the kidney with aging. Cortical parenchyma, functional nephron number, renal blood flow and glomerular filtration rate (GFR) decrease. Due to these aging-related changes in the kidney and increased comorbid diseases, the physiological reserves of the kidney decrease and the adaptation response to stressors deteriorates; many renal diseases, especially acute kidney injury, are observed more easily and frequently3-5.
Renal biopsy is the sampling of renal tissue by methods such as percutaneous renal biopsy or fine needle aspiration. Renal biopsy is the gold standard in the diagnosis, treatment and prognosis of renal parenchymal diseases6. In the elderly population, indications for renal biopsy in nephrology practice are similar to that in all age groups. Kidney biopsy indications include nephrotic syndrome and non-nephrotic proteinuria, acute kidney injury, isolated microscopic/macroscopic hematuria, coexistence of proteinuria-hematuria, systemic diseases with loss of renal function, and renal allograft dysfunction7.
There are special considerations when making the decision to perform renal biopsy in elderly patients. As with many invasive procedures in the elderly population, renal biopsy may have a high complication rate due to factors such as physiologic changes related to aging, accompanying comorbid diseases, polypharmacy and contrast exposure8.
The number and proportion of the elderly population in Turkey and the world is increasing rapidly. It is estimated that there were 783 million elderly people worldwide in 2022 and that this number will increase to 1.3 billion in 2040. In Turkey, the elderly population, which was 7.18 million in 2018, increased by 21.4% in the last five years and reached 8.7 million in 2023, and this figure is expected to increase to approximately 16 million in 20409. In parallel with the increasing elderly population, the number of renal biopsies in the elderly is gradually increasing10, 11. In our country, studies evaluating the results of renal biopsy in the elderly are limited in number. In this study, we aimed to investigate the indications, complications, pathologic results and treatments of renal biopsy in elderly patients.
MATERIALS AND METHODS
Our study is a retrospective descriptive cross-sectional study among patients aged 65 years and older, who underwent ultrasonography-guided renal biopsy using a 16-18 G automatic biopsy needle between January 01, 2004 and January 01, 2023 in the department of nephrology of our hospital, a tertiary care university hospital.
Inclusion criteria were determined as;
- Having kidney biopsy performed,
- Being 65 years of age or older and being followed up in the nephrology clinic of our university.
Exclusion crtiteria were as follows;
- Having transplanted kidney biopsies,
- Undergoing biopsy for malignancy,
- Having kidney biopsy procedure that was performed in our hospital, but being followed up and treated in another hospital,
- Having unmeasured proteinuria in 24-hour urine (followed up with spot urine protein/creatinine ratio),
- Having insufficiently recorded available data,
- Being younger than 65 years of age.
Demographic information, biopsy date, chronic diseases, indications for biopsy, pre-biopsy laboratory data, complications after biopsy, pathology results, post-biopsy treatments and complications after treatment were recorded from patient files and hospital information system. Indications for biopsy were grouped as nephrotic proteinuria, acute kidney injury, non-nephrotic proteinuria and micro/macrohematuria. Nephrotic proteinuria was defined as protein excretion above 3.5 g/day in 24-hour urine, acute kidney injury as serum creatinine level ≥0.3 mg/dL or ≥0.5-fold increase from baseline in the last 48 hours or ≥1.5-fold increase from baseline in the last 7 days or urine output less than 0.5 mL/kg/hour in the last 6 hours, non-nephrotic proteinuria as the presence of proteinuria below 3.5 g/day without accompanying hematuria, and micro/macrohematuria as the presence of hematuria without accompanying proteinuria. Proteinuria was considered as the presence of more than 500 mg of protein in the 24-hour urine, microscopic hematuria was defined as the presence of ≥3 erythrocytes in each large magnification field on microscopic examination of urine sediment, and macroscopic hematuria was defined as hematuria that caused discoloration in the urine that was visible to the naked eye. Serum creatinine, albumin, uric acid, estimated GFR, 24-hour urine proteinuria and hematuria were recorded before biopsy. Creatinine clearance was calculated according to the Cockcroft and Gault12 and MDRD-4 (Modification of Diet in Renal Disease-4)13 formulas. Pathologic classification was made into 5 groups as primary glomerulonephritis (PGN), secondary glomerulonephritis (SGN), tubulointerstitial nephritis (TIN), vascular diseases and unclassified cases.
For all patients, renal biopsy specimens examined by light microscopy and immunofluorescence microscopy were considered adequate if there were at least 10 glomeruli in the sample14. Immunosuppressive treatments given to the patients after biopsy were recorded. Immunosuppressive treatments were grouped as glucocorticoids, cyclophosphamide, mycophenolate mofetil.
Complications developing after biopsy were grouped as major and minor. Complications such as bleeding requiring transfusion, macroscopic hematuria, penetration to liver, spleen, pancreas, intestine and gallbladder, pneumothorax, hemothorax, development of arteriovenous fistula and death were considered major complications and complications such as pain and perirenal hematoma were considered minor complications.
The study was conducted after obtaining the necessary permissions from Atatürk University Faculty of Medicine Clinical Research Ethics Committee (decision no: B.30.2.ATA.0.01.00/862, date: 26.10.2023).
Statistical Analysis
Data were recorded into the Statistical Package for the Social Sciences 23.0 package program and analyses were performed using the same program. Data were presented as number (n), percentage (%) and median (minimum-maximum). Descriptive statistics were given as median and minimum-maximum median for nonparametric continuous data. Categorical data were presented as frequencies with percentages in parentheses and compared using the chi-square test. The Mann-Whitney U test was used to determine the differences in the rating scores, which were considered as continuous data. A probability value less than 0.05 was considered to be statistically significant.
RESULTS
In our study, 66 geriatric patients who underwent renal biopsy were retrospectively evaluated. The median age of the patients was 73.0 (IQR; 68.8-79.0) years and 44 (66.7%) were male. When the patients were evaluated in terms of chronic systemic diseases, HT (83.3%), DM (24.3%), coronary artery disease (22.7%) and CKD (21.2%) were detected to be the most common diseases. Demographic characteristics and underlying diseases of the patients are shown in Table 1.
When the patients were evaluated in terms of indications for renal biopsy, nephrotic proteinuria (n=37, 56.1%) was found to be the most common indication for renal biopsy. The second most common indication for biopsy was acute kidney injury (n=16, 24.2%). The median pre-biopsy serum creatinine, albumin and proteinuria levels were 2.14 (0.99-4.63) mg/dL, 2.51 (2.10-2.95) g/dl, and 4770 (1156-7644) mg/day, respectively. Indications for renal biopsy and pre-biopsy laboratory data are presented in Table 2. None of the patients developed major or minor complications after biopsy.
PGN (62.1%) was the most common biopsy result, followed by SGN (21.2%) and TIN (12.1%). Membranous glomerulonephritis (MGN) was the most common primary glomerular disease (39.4%), while secondary amyloidosis was the most common secondary glomerular disease (9.1%). When pathology results were evaluated without differentiating between primary and secondary GN, the most common diagnoses were revealed to be MGN (39.4%), focal segmental glomerulosclerosis (FSGS) (12.1%), secondary amyloidosis (9.1%), and chronic TIN (9.1%) (Table 3).
Immunosuppressive treatment was administered to the patients most frequently (54.5%) after biopsy. Glucocorticoids (48.5%) and cyclophosphamide (22.7%) were the most common immunosuppressive treatments. The treatments given to the patients after biopsy are presented in Table 4.
DISCUSSION
Renal biopsy is the gold standard for determining whether glomerular lesions are acute or chronic, reversible or treatable, regardless of age14. Identification of renal lesions by biopsy enables more accurate identification of renal pathologies without being dependent on diagnostic methods such as creatinine-based GFR (eGFR) calculations, which can be affected by many age-related factors. Thus, it allows the selection of the right treatment modalities. It helps to avoid inappropriate treatments, especially immunosuppression, and related complications. Early diagnosis and correct treatment may be of vital importance in the elderly, especially in the frail elderly population. In the literature, it has been shown that renal damage tends to become chronic faster in the elderly compared to young people due to low renal reserve and decreased renal mass and function15.
In our study, which included a total of 66 geriatric patients who underwent kidney biopsy, it was observed that kidney biopsy was performed more frequently in male patients (66.7%), in line with the literature16, 17. It is known that, starting from the fourth decade of aging, there is a decrease in kidney size due to a decrease in the renal cortical parenchyma and the number of functional nephrons. It has been shown that the decrease in kidney size is greater in the male gender3. It has also been shown that gender is one of the determinants of age-related decline in renal functions, that most of the damage that occurs in the kidney with age is related to androgen production, and that medical castration can slow the progression of these changes18, 19. Kidney biopsy is performed more frequently in men, which may be due to the fact that renal functions and renal parenchyma loss are greater in men and the number of cases is lower. In our study, the most common chronic systemic diseases in patients who underwent kidney biopsy were found to be HT (83.3%), DM (24.3%), CAD (22.7%) and CKD (21.2%). Studies have reported that HT is the most common chronic disease in elderly patients who underwent biopsy, with rates ranging from 24.1% to 78%20-24. The rate of DM was reported to be 15.3% by Ozturk et al.20 and 29.4% by Tuğcu et al.23, similar to that in our study. As renal reserves decrease with aging, additional diseases that may cause kidney disease, especially DM, atherosclerotic vascular diseases and HT, facilitate the development of new kidney pathologies. Studies have shown that approximately 5-10% of the elderly have a decrease in kidney function with age, despite the absence of any accelerating factors, while no measurable decrease is detected in 30% of them25. eGFR can be expected to decrease with aging. However, normal eGFR values have also been detected, especially in normotensive elderly people5. This shows us the contribution of chronic comorbid diseases to the progression of renal dysfunction.
Although biopsy indications vary on a national or center basis in the literature, it has been reported in many biopsy series that the most common indication in the elderly is nephrotic proteinuria11, 23, 24, 26, 27. In our study, nephrotic proteinuria (56.1%) was found to be the most common biopsy indication in the elderly. Studies conducted in our country have reported that the rate of kidney biopsy performed with the indication of nephrotic proteinuria in the elderly is between 41.38% and 60%11,21-24,26,28. The fact that nephrotic proteinuria is the most common biopsy indication may be due to the fact that the elderly see the symptoms as a part of the natural process of aging and apply to the hospital late. Similar to our study, studies have shown that acute kidney disease (AKD) is the second most common biopsy indication in the elderly and that biopsy due to AKD is performed more frequently in the elderly than in young people21, 23, 24, 29. Additionally, in two studies conducted in elderly patients, AKD was reported to be the most common indication30, 31. Studies have proven that the incidence of AKD increases with age32. Among the elderly, the frequency of AKD increases significantly as age increases33. The elderly are prone to kidney damage due to structural and functional changes in the kidney with aging, increased comorbid diseases and polypharmacy4. Increased biopsy rates due to AKD in the elderly may be related to the fact that the elderly are more prone to AKD and have a higher probability of prolonging the duration of AKD and becoming chronic due to their low renal reserves.
In our study, similar to studies conducted in our country21, 22, 24, 34, PGN (62.1%) was the most frequently detected biopsy result, followed by SGN (21.2%) and TIN (12.1%), respectively. In studies conducted abroad and involving large patient groups, it has been shown that PGN is the most common disease in the elderly, followed by SGN and TIN35. In the study by Harmankaya et al.24 in 2015, in which they evaluated 98 elderly patients, the most frequently detected PGN type was stated as MGN (14.3%). This was followed by FSGS (12.2%) and crescentic GN (6.1%)24. In the study by Tuğcu et al.23 in which kidney biopsies of 109 elderly patients were evaluated, the most common causes of PGN were found to be FSGS (13.8%), MGN (10.1%) and pauci-immune glomerulonephritis (PIGN) (5.5%), respectively. In the study of Hur et al.34, in which 121 elderly patients who underwent kidney biopsy were included, it was reported that the most common PGNs were MGN (14.8%), crescentic GN (9.92%) and FSGS (9.92%). In another study conducted by Ozdemir et al.26 on 93 elderly patients and presented in 2022, MGN (42.8%) was found to be the most common pathology among PGNs. In the study conducted by the Turkish Nephrology Association ‘Glomerulonephritis Study Group’, in which 47 centers participated and which included the largest number of biopsy series regarding PGNs in our country, only primary glomerular diseases were included and 3,858 patients, 262 of whom were elderly, were evaluated. In this study, MGN (40.2%), FSGS (17.4%) and crescentic GN (15.1%) were most commonly observed in the elderly. In addition, in the period covering 2017 and before, crescentic GN (23%) was the second most common type of GN and FSGS (15.2%) was the third most common type of GN. It has been stated that as of 2017, FSGS has become the second most common GN and the frequency of FSGS in the elderly is gradually increasing11. Studies have shown that the incidence of FSGS in the elderly is increasing worldwide23, 36. This increase has been attributed to increased awareness of FSGS and an increase in the incidence of FSGS in the elderly secondary to diseases such as HT and age-related nephropathy30. In studies conducted abroad, while MGN stands out as the most frequently detected PGN in Spain37, Czech Republic38, Italy39 and England40 in Europe, the second one changes FSGS, minimal change disease and IgA nephropathy (IgAN). In studies conducted outside Europe, PGN and MGN were most frequently detected as in all other studies in Brazil41, South Africa42, Ireland43, China44, Japan35 and the United States30. It has been reported that FSGS and IgAN are the second most common. The distribution of glomerulonephritis types varies from country to country and in different regions of the same country, depending on age, gender, ethnicity, geographical region, clinicians’ attitudes towards indications and years. As in recent studies conducted in our country11, 24, in our study, MGN (39.4%) was found to be the most common and FSGS (12.1%) was the second most common glomerular pathology, both among PGNs and among all patients who underwent biopsy. In terms of the frequency of PGN, the results of our study are similar to those reported by recent large-scale studies conducted in our country11, 26.
In the study conducted by Tuğcu et al.23, while the most common cause of SGN was found to be secondary amyloidosis (22.9%), diabetic nephropathy (DN) was reported to be the second most common and lupus nephritis (LN) was reported to be at the rate of 3.6%. In the study conducted by Harmankaya et al.24, amyloidosis was found to be the most common SGN with the rate of 15.3%, followed by PIGN (8.2%) and DN (5.1%). Hur et al.34 found that amyloidosis (19.1%) was the most common cause of SGN, followed by GNs due to vasculitis (4.96%) and LN (1.65%). In European, American and Asian countries, it has been reported that SGN due to LN is more common than secondary amyloidosis and vasculitis30, 37, 39, 42. The frequent occurrence of secondary amyloidosis in our study and in our country is due to the fact that Familial Mediterranean Fever is an endemic disease in Turkey and the most common cause of secondary amyloidosis45. In our study, the frequency of DN is low and the rates are consistent with the literature23, 24, 34. Although DN is the most important cause of ESRD, it is rarely observed in biopsy results. The reason for this is that the diagnosis of DN is made clinically and biopsy is not preferred unless there is additional evidence suggesting PGN46. In our study, although 24.3% of the patients who underwent biopsy were diagnosed with DM, the rate of patients diagnosed with DN as a result of biopsy was 3%.
Complications seen after kidney biopsy include pain, hematoma, macroscopic hematuria, major hemorrhage (bleeding requiring transfusion or radiological/surgical intervention), septicemia, and arteriovenous fistula formation47. Although theoretically there is no difference in the indications for biopsy between young and old patients, biopsy can be avoided in the elderly due to concomitant systemic diseases, low life expectancy, clinicians’ avoiding biopsy and immunosuppressive treatment complications, and the thought that biopsy will show findings of chronic changes such as interstitial fibrosis and atrophy rather than a treatable lesion27, 30. The frequency of complications after kidney biopsy varies due to patient selection, procedural techniques, variability in complication definitions, and differences in post-procedure monitoring time, but is on average 5-10%47. Serious side effects requiring surgical intervention occur at a rate of <1% and the mortality rate is <0.1%27. Kajawo et al.48 performed a meta-analysis and they stated that complication rates decreased after biopsy procedures performed under ultrasound guidance and automatic needles. In the literature, it has been reported in series including large patient groups that age is not a risk factor for biopsy complications and that there is no increase in the risk of complications in the elderly48, 49. It was observed that there were no complications after the kidney biopsies performed in our study. It is thought that the reason why no complications were observed in our study may be related to the fact that biopsies were performed with automatic biopsy needles under ultrasound guidance, bleeding control was routinely performed with ultrasound during follow-up, protective measures were taken more frequently as the risk of complications was higher in the elderly, and the number of cases was low. Inadequate diagnosis and treatment of renal parenchymal diseases is strongly associated with the risk of ESRD and increased morbidity and mortality in the elderly50. Pathological diagnoses made by kidney biopsy in elderly patients can be controlled with appropriate treatment. In this way, negative health consequences and unnecessary treatment burden in elderly patients can be avoided. Kidney biopsy, which is a reliable procedure with low complication rates, should not be avoided in the elderly.
Study Limitations
The strength of our study is that it is the first study examining elderly kidney biopsies in our region. The limitations of our study are that it was retrospective and conducted in a single center.
CONCLUSION
As a result, the most common indications for kidney biopsy in the elderly are nephrotic proteinuria and AKD, and it is the most common reason for biopsy in the elderly. PGN is most commonly seen in the elderly, and MGN and FSGS are observed more frequently. Among SGN, amyloidosis and LN are the most common. Kidney biopsy is the gold standard method in the diagnosis of renal parenchymal diseases and is a reliable procedure with low complication rates in the elderly. Kidney biopsy should not be avoided in the elderly if clinically necessary.
