Introduction:
Lupus nephritis is a secondary glomerulonephritis which occurs when SLE involves the kidney. It is seen in 50 to 60% of SLE and is a strong determinant of morbidity and mortality. SLE commonly affects females primarily women of child bearing age group. One of the most important poor prognostic factor associated with an increased rate of mortality is the development of lupus nephritis. The severity of the disease depends on age, sex, race and other environmental factors. Historically male gender has demonstrated severe form of the disease according to various studies. Time from the disease onset and establishing a clinical diagnosis of lupus nephritis was described to be more prolonged in males due to overlooking of SLE symptoms . More random presentation of SLE in males leads to less awareness and underestimating of SLE symptoms in male patients group. Hence our study was to analyze the clinical presentation and histopathological profile of lupus nephritis in males in comparison to females.
Methods:
Two cohorts of biopsy proven lupus nephritis from 2011 to 2022 comprising 50 males and 50 females in each cohort were retrospectively analyzed. The diagnosis of LN was exclusively histologic, through renal biopsy. After data collection the male cohort was compared with the female patients selected from the same registry as the male patient, and patient’s age, year of LN diagnosis, clinical presentation, Laboratory parameters, histological findings were taken into account.
Results:
The mean age of presentation of LN was 28.48 ±11.13 in females and 25.70 ±9.27 in males. Our study demonstrated a younger age presentation of LN in males. Both male and female population most commonly presented in age group 15-30 years. About 50% of males had LN as initial presentation whereas only 30% of females had LN as their first presentation. Musculoskeletal or mucocutaneous manifestation were observed in 70% of females and 60% of males. In our study the most common extra renal manifestation other than the mucocutaneous/ musculoskeletal involvement was hematological (34% and 40% of females and males respectively). 60% of females and 48% of males had a hemoglobin less than 10, among which 10 % of each sex had severe anemia. Leukopenia observed was 10% and 8% in females and males respectively. Thrombocytopenia was noted in 30% of females and 24% of males. Other common extra renal involvement were serositis, cardiac and pulmonary with CNS being least common in both the cohorts. Significant difference in the incidence of DM being more common in females compared to males. Hypothyroidism was equally common in both sex (18%). Significant difference in the Incidence of Hypertension in males (44%) compared to females (24%) with higher mean Systolic blood pressure/Diastolic blood pressure in males.
In our study, male patients presented late after the initial musculoskeletal/ mucocutaneous or other extra renal symptoms. Symptoms pertaining to LN per se showed edema as the most common presenting symptoms in both males(90%) and females(70%). The other common presentations were frothuria, hematuria, reduced urine output and shortness of breath. Only 10% males were asymptomatic but significant number of females had asymptomatic presentation (20%).Their indication of biopsy were presence of subnephrotic proteinuria. In our study nephrotic syndrome was the most common presentation in males (40%) and females(44%). Similarly the Rapidly progressive renal failure(RPRF) presentation was also same in both males (20%) and females (22%). Hematuria was significantly common in males (72%) compared to females (48%) in our study. Nephrotic range proteinuria (>3.5 g) was seen commonly in males (54%) compared to females (38%).In females 58% patients had subnephrotic proteinuria. The average 24 hr urine protein was 4.13± 2.49 in males and 3.62 ± 2.28 in females. The mean presentation creatinine in males and females were 1.82 ±1.65 and 1.71±2.28. Most patients had serum albumin in the range of 2.1 to 3.5 which was similar in both the cohorts. Assessment of Immunological profile in our study showed sensitivity of Antineutrophilic antibody(ANA) was more in females (96%) compared to males (80%). The sensitivity of Anti dsDNA was more in females (90%) compared to males (74%). Complement analysis in our study showed low C3 in almost 92% of females and 90% of males. C4 was low in almost 64% of females and 66% of males.
Observation of histopathological class of LN in our study showed Class IV lupus as the most common histological class observed in both males and females followed by class V. Presence of crescents was seen in 24% of females and 26% of males. 22% and 28% had no IFTA(Interstitial fibrosis and tubular atrophy) among female and male cohorts.Very few patients had TMA(Thrombotic microangiopathy ) changes (14% and 10% in females and males respectively).
Conclusions:
In our study, focusing on gender differences of clinical spectrum and histopathological profile we could conclude that men and female had a near similar presentation except for Hypertension and degree of proteinuria being more common and severe in males. Our studies could not demonstrate the increased severity of LN in males at the time of presentation. Assessing long term treatment outcomes and response to treatment could further clear the myth of male gender as a risk factor for severe LN.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.