This narrative review was guided by a broad structured search of PubMed/MEDLINE, Web of Science, Scopus, and Embase. Search terms combined descriptors for leprosy (leprosy, Hansen disease, Mycobacterium leprae) with renal terms (kidney, renal involvement, acute kidney injury [AKI], renal failure, GN, chronic kidney disease, urinary abnormalities). The database exports contained 565 records in total: 69 from PubMed/MEDLINE, 161 from Embase, 182 from Scopus, and 153 from Web of Science. Because the objective was a current narrative synthesis rather than a formal systematic review, study selection prioritized publications that clarified the historical renal spectrum, MDT-era urinary or functional abnormalities, reaction-associated risk, biomarker plausibility, differential diagnosis, or practical monitoring implications. Institutional guidance relevant to leprosy care and reactional states was also reviewed. Among the 36 sources cited in the final manuscript, 26 directly addressed the renal scope of the review, including renal involvement, kidney function, urinary abnormalities, renal histopathology, amyloidosis, renal biomarkers, renal case phenotypes, or drug-associated kidney injury in leprosy. The remaining 10 references were used to contextualize the review, including contemporary leprosy epidemiology, global guidance, reactional-state characterization, endothelial biology, and treatment-related considerations. A simplified narrative-selection flow diagram was added as Fig. 1.

By design, this approach does not provide the exhaustive reproducibility of a systematic review and may be influenced by heterogeneity in study design, era, and renal definitions across the literature; however, it was chosen to support a clinically oriented synthesis of a field in which historical pathology-based reports and biomarker-focused studies must be interpreted together rather than in isolation. The search strategy and practical selection logic are provided in Supplementary Tables 1 to increase transparency and reduce selective citation bias.

When available, quantitative renal findings were extracted descriptively, including the frequency of renal dysfunction, urinary abnormalities, histopathologic lesions, biomarker associations, and within-cohort changes after MDT initiation. Because of substantial heterogeneity in study design, population, era, renal definitions, reactional status, treatment exposure, and outcome ascertainment, no pooled estimate or formal meta-analysis was attempted.

Understanding renal involvement in the MDT era requires a brief return to the historical literature that first defined the renal spectrum of leprosy [1, 10,11,12,13,14,15]. These earlier studies established that renal involvement was heterogeneous, clinically relevant, and closely linked to inflammatory burden, thereby providing the reference framework against which the MDT-era phenotype must now be interpreted [1, 10,11,12,13,14,15]. Their value today is not to provide contemporary prevalence estimates, but to define the lesion patterns and inflammatory contexts that remain clinically relevant.

Historically, recognition of renal involvement in leprosy did not begin with biopsy, but with functional assessment [10]. As early as 1973, Gutman and colleagues demonstrated defects in urinary acidification and concentrating ability, indicating that the kidney could be affected even outside the setting of florid glomerular disease or end-stage failure [10]. This remains conceptually important because it broadens renal involvement beyond late glomerular disease, nephrotic syndrome, or autopsy-defined pathology [1, 10].

The second half of the 1970 s shifted attention from function to structure [11, 12]. The ultrastructural study by Date et al. revealed proliferative GN with subendothelial and subepithelial deposits, whereas the histopathologic series by Gupta et al., based on 50 kidney biopsies, showed that renal involvement in leprosy was neither uniform nor restricted to a single anatomic pattern [11, 12]. Together, these studies supported a heterogeneous nephropathy in which host-mediated mechanisms appeared more relevant than direct bacillary injury alone [1, 11, 12, 14]. This distinction remains useful because it helps explain why renal disease may be attenuated in contemporary practice without becoming clinically irrelevant.

In the 1980 s, this interpretation gained greater consistency [13, 14]. Phadnis et al. described membranous and membranoproliferative lesions, amyloidosis, and tubulointerstitial nephritis (TIN), whereas Chugh et al. added immunofluorescence evidence of immunoglobulin and complement deposits [13, 14]. Taken together, these studies allowed the classical nephropathy of leprosy to be organized into three principal axes: probable immune-mediated GN, amyloidosis as a consequence of sustained chronic inflammation, and interstitial lesions often aggravated by secondary infection or therapeutic exposure [1, 13,14,15]. The mechanistic inference, however, should remain on the appropriate scale: the classical literature strongly supports immunopathologic plausibility, but not a conclusive demonstration of mechanism [1, 13, 14]. More recent clinical and biopsy-based reports reinforce this heterogeneity, describing infection-related glomerulonephritis, IgA-dominant infection-related glomerulonephritis, immune-complex glomerulonephritis after type 2 lepra reaction, amyloid A (AA) amyloidosis, rifampicin-associated tubular injury, and vasculitic or tubulointerstitial patterns in patients with leprosy [16,17,18,19,20,21]. The clinical bridge between this lesion-based literature and contemporary monitoring is reactional inflammation, particularly erythema nodosum leprosum (ENL) [22,23,24,25,26,27].

The work of Drutz and Gutman had already linked GN to ENL, and subsequent studies documented worse kidney function during reactional phases, including partial improvement after resolution of the reaction [22,23,24,25,26,27]. Across the older functional and pathology-based literature, ENL emerges as the most consistent clinical correlate of renal vulnerability [22,23,24,25,26,27]. For current practice, this association is most useful as a risk-enrichment signal: renal abnormalities arising during recurrent or severe reactional inflammation should not be dismissed as incidental, even if overt nephropathy is uncommon [1, 3, 22,23,24,25,26,27].

Finally, the autopsy literature defined the severe end of the pre-MDT renal spectrum [28]. In the retrospective series of 199 autopsies analyzed by Nakayama et al., renal lesions were frequent, with amyloidosis, GN, and TIN being particularly prominent [28]. Amyloidosis was especially associated with lepromatous forms, recurrent ENL, and trophic ulcers, whereas kidney failure was an important cause of death [28]. These data do not define the current renal phenotype; rather, they provide the historical backdrop against which it must be reinterpreted [1, 28]. The contemporary task is therefore not to transpose autopsy-era severity to all MDT-treated patients, but to recognize how prolonged multibacillary disease, recurrent reactions, and chronic inflammatory burden may still define a renal-risk context. The scarcity of systematically phenotyped contemporary renal-pathology studies is a limitation of the field; for that reason, historical lesion-based evidence must be interpreted alongside more recent functional, cohort, and biomarker data. Selected quantitative renal signals supporting this historical-to-MDT-era transition are summarized in Table 1.

The advent and consolidation of MDT from the early 1980 s onward may have altered not the existence of renal involvement in leprosy, but its usual clinical expression [1, 3, 29, 30]. Much of the classical renal literature emerged from settings characterized by prolonged untreated disease, higher cumulative inflammatory burden, recurrent reactional episodes, and delayed diagnosis, all of which may have amplified the visibility of amyloidosis, nephrotic syndrome, and advanced kidney failure [1, 10,11,12,13,14,15, 22, 28]. Accordingly, the historical spectrum remains indispensable, but it should not be transposed uncritically to the contemporary bedside [1, 3]. A more defensible current interpretation is that renal involvement persists in the MDT era, but may more often appear as earlier, milder, and context-dependent urinary or functional abnormalities shaped by multibacillary disease, reactional activity, and superimposed nephrotoxic or hemodynamic stressors [3,4,5, 29, 30].

That change in phenotype should not be mistaken for irrelevance [1, 3, 29, 30]. In the Brazilian retrospective series of 461 patients, serum creatinine > 1.4 mg/dL was documented in 8.6%, and proteinuria, hematuria, and hemoglobinuria were significantly more frequent in lepromatous disease; even nephrotic-range proteinuria was reported in 2.1% of the 138 lepromatous cases [29]. For a current review, the value of these data is primarily clinical: they show that measurable renal abnormalities persisted in routine care after MDT became available and continued to cluster in patients with higher bacillary burden [29, 30]. The study should nevertheless be interpreted cautiously, as its retrospective design does not allow reliable distinction between persistent injury, transient reaction-associated abnormalities, and treatment-related changes [29]. Its main value is therefore clinical: it argues against the mistaken assumption that renal involvement became negligible in the MDT era [29, 30].

The most informative bridge between the classical and contemporary eras is the prospective study of 189 patients evaluated before MDT and again after 3 and 8 months of therapy [3]. At baseline, microhematuria and microalbuminuria were present in 7.5% and 9.6% of cases, respectively, whereas elevated serum creatinine was found in 34%, with higher values occurring more often in men, patients with hypertension, frequent non-steroidal anti-inflammatory drug (NSAID) users, and those with ENL [3]. Among patients with ENL, the proportion with elevated creatinine fell from 45.5% at diagnosis to 18% after 3 months and 9% after 8 months of MDT [3]. Read carefully, this study should not be reduced to a causal claim that MDT alone improves kidney function [3]. Its more useful message is that renal abnormalities in leprosy may be dynamic and influenced by infection control, reaction management, comorbidities, NSAID exposure, and other concurrent renal stressors [3,4,5, 29,