Histopathology pattern and survival analysis of patients with kidney biopsy in the top end of Northern Australia from 2007 to 2020

Demographics

In. brief, a total of 602 renal biopsies performed between June 2007 and June 2020 was collected. 185 transplanted renal biopsies were excluded in the early stage of analysis. 25 biopsies were excluded from analysis due to suboptimal histology sample. There were 364 native renal biopsies that we included in the analysis as shown in Fig. 1.

Fig. 1figure 1

Flow chart of patient selection

Figure 2 shows the patient demographics of renal biopsies according to sex and indigeneity. The age at the time of kidney biopsy ranged from 17 years old to 89 years old, with male (210 cases, 39.6%%) to female (320 cases, 60.4%) of the full cohort, with mean age at the time of biopsy was 49.2 ± 15.5 years for female and 52.7 ± 15.3 years. The mean difference between age between male and female was 3.5 years old (p = 0.024). Indigenous female had the greatest number of renal biopsies (n = 231 43.6%), compared to the three other main groups. Most kidney biopsies were done in the age group 40–49 years old (18.8% indigenous male, 43.5% indigenous females, 17.6% non-indigenous males and 20.0% non-indigenous females). Most indigenous males who underwent renal biopsies were from the age group of 50 to 59 years old (n = 25) while most indigenous females were from the age group of 40–49 years old (n = 37). Most non-indigenous males had renal biopsy at the age of 60–69 years old (n = 21) while most non-indigenous females had renal biopsy at the age of 30–49 years old (n = 34).

Fig. 2figure 2

Patient demographics of renal biopsies according to sex and indigeneity. *Footmark: I: indigenous; NI: non-indigenous

Clinical indications

Figure 3 shows the clinical indications of renal biopsy. Sub-nephrotic proteinuria was the most common clinical indication for kidney biopsy, accounting of 47.8% (n = 160) of all cases, followed by nephrotic syndrome (n = 120, 35.8%), nephritic syndrome (n = 102, 30.4%), acute kidney injury (n = 94, 28.1%), unexplained renal impairment (n = 30, 9.0%) and others (n = 15, 4.5%). The ‘others’ category included any kidney biopsy in which the treating nephrologist did not specify the indication of the procedure on pathology request form.

Fig. 3figure 3

Frequency of renal biopsy according to the clinical indication

Pathological diagnosis

Diabetes nephropathy (DN) was the most common pathological finding, accounting for 12.8% (n = 71), followed by focal segmental glomerulosclerosis (FSGS) (n = 47, 8.5%), glomerulomegaly (n = 44, 7.9%), IgA nephropathy (n = 44, 7.9%) and hypertensive renal disease (n = 14, 2.5%). Post-infective glomerulonephritis (PIGN) contributed to 4.5% (n = 25) of the renal biopsy in the Northern Territory.

Based on the International Society of Nephrology/Renal Pathology Society classification, the cohort of lupus nephritis (LN) was categorised as follows: class I (n = 22, 4.0%), class II (n = 8, 1.4%), class III (n = 11, 2.0%), class IV (n = 17, 3.1%) and class V (n = 12, 2.1%).

Diabetic nephropathy was the most common diagnosis among indigenous males (n = 20, 2.17%) and indigenous females (n = 39, 54.93%). Most non-indigenous males (n = 17, 38.64%) have IgA nephropathy while most non-indigenous females (n = 13, 27.66%) had focal segmental glomerulosclerosis (FSGS).

In FSGS, indigenous females contributed to the highest count (n = 15, 31.91%), followed by non-indigenous females (n = 13, 27.66%), indigenous males (n = 11, 23.40%) and non-indigenous males (n = 8, 17.02%).

Among 25 people with PIGN, 60% (n = 15) were from indigenous population, which consists of 10 indigenous males and 5 indigenous females. Males (n = 15) had a higher incidence of PIGN than females (n = 10).

The majority of IgA nephropathy was found in non-indigenous males (n = 17, 38.64%). Indigenous females and non-indigenous females contributed to the same number (n = 10, 22.73%). Only 7 indigenous males (n = 7, 15.91%) were diagnosed with IgA nephropathy.

Among the patients with normal renal biopsy, the number from each patient group was similar. 4 indigenous males and 3 indigenous females had normal biopsies while 3 non-indigenous males and 4 non-indigenous females had normal renal biopsies in RDH.

No indigenous population were diagnosed with AL amyloid, anti GBM, scleroderma, light chain nephropathy and Alport Syndrome. The complete histopathology pattern of native renal biopsy conducted in the Top End is demonstrated in Fig. 4.

Fig. 4figure 4

Histopathology pattern of renal biopsy. Footmark: IgAN: IgA nephropathy; ATN: acute tubular necrosis; AIN: acute interstitial necrosis; MCD: minimal change disease; FSGS: focal segmental glomerulosclerosis; MGN: membranous glomerulonephritis; AAV: ANCA-associated vasculitis; PIGN: post-infective glomerulonephritis; Prolif GN: proliferative glomerulonephritis; MPGN: membranous-proliferative glomerulonephritis; DMN: diabetic nephropathy; TBMN: thin-basement membrane nephropathy; TMA: thrombotic microangiopathy; SRC: Scleroderma renal crisis; CIN: Contrast-induced nephropathy; C3GN: C3 glomerulonephropathy; IFTA 10–30: Interstitial fibrosis and tubular atrophy; LN: lupus nephropathy; FGN: Fibrillary glomerulonephritis; LCN: Liver cirrhosis-related nephropathy; AS: Alport Syndrome; HRD: Hypertensive renal disease; RI: Renal ischemia

Survival

In total there were 64 deaths (18.2%) and 101 patients who undergone at least 1 dialysis episode (28.8%). Overall, Indigenous population had a significantly poorer survival than non-indigenous population based on Fig. 5. The univariate hazard ratio of indigenous status was 2.41 (95% CI: 1.39–4.18, p = 0.002). The hazard ratio from multivariate Cox proportional hazard model survival adjusting for indigeneity, age and sex are shown in Table 2. There was a very strong evidence to show that indigeneity status and high age group were significant factor that led to poorer outcome. Male had slightly worse outcome than female (HR 0.60, 95% CI 0.36–0.98, p = 0.043).

Fig. 5figure 5

Kaplan–Meier survival curves of patients underwent kidney biopsies by Indigenous status

Table 2 Multivariate Cox proportional hazard model survival, adjusting for indigenous status, sex and age

Figure 6 shows Kaplan–Meier survival curve by histology of kidney biopsy. For practical purpose, we were focusing on the main histology including diabetic nephropathy, focal segmental glomerulosclerosis, hypertensive renal disease and IgA nephropathy. Other histology diagnosis was categorized as ‘others’. Diabetic nephropathy was the reference group and the other groups were compared accordingly. The risk of death was significantly lower than the Diabetic Nephropathy group. Patients with FSGS had 59% lower chance of death (HR 0.41, 95% CI 0.17–0.97, p = 0.0043) while patients with hypertensive renal disease had 64% lower chance of death (HR = 0.36, 95% CI 0.12–1,06, p = 0.0063).

Fig. 6figure 6

Kaplan–Meier survival curve by histology of kidney biopsy

Figure 7 and Table 3 shows the survival analysis for patients undergone dialysis, sorted by indigenous status. There was a very strong statistical significance that indigenous population who had dialysis performs poorly compared to their non-indigenous counterpart (HR 2.37, 95% CI 1.53–3.67, p < 0.001).

Fig. 7figure 7

Kaplan–Meier curve for patients undergone dialysis, by indigenous status

Table 3 Shows multivariate cox proportional hazard model survival of patients with main histology diagnosis (Reference group: Diabetic Nephropathy)

As shown in Fig. 8 and Table 4 shows the survival analysis for population who had dialysis, stratified by their indigenous status and histology diagnosis. The difference in the survival of dialysed patients was not statistically significant for FSGS, HRD and IgA nephropathy.

Fig. 8figure 8

Shows Kaplan–Meier curve for patients who had dialysis, stratified by their indigenous status and histology diagnosis

Table 4 Shows survival analysis for population who had dialysis, stratified by their indigenous status and histology diagnosis (Diabetic nephropathy as the reference group)

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