**4.1 Role of renal biopsy**

Renal biopsy is the gold standard for the diagnosis and current classification of LN. The histological findings may assist physicians to optimise therapeutic strategies in individual patients, including assessing disease activity and/or chronicity for guidance to escalate or de-escalate immunosuppression accordingly. It is an invasive procedure with potential risks, most notably bleeding; however, given the lack of available biomarkers to identify disease activity, it remains an irreplaceable tool and mainstay of current management in LN.

Indication for a renal biopsy includes significant proteinuria of >0.5 g/day (or equivalent), certain unclear acute elevation of serum creatinine level, and in patients with severe disease relapse (**Table 1**) [47]. Biopsy is rarely done in patients with isolated haematuria or proteinuria of <0.5 g/day; hence, class I LN is rarely seen in the histology. Performed by either experienced nephrologist or interventional radiologist, adequate tissue is obtained in >95% of times.

Given the location of kidney where no direct compression can be performed post biopsy, bleeding (as detected by routine CT scan or ultrasound post biopsy) was found to be common, ranging in 57–91% of patients [48]; however, the actual incidence of clinically important bleeding is small. Meta-analysis of 34 relevant studies found low rates of macroscopic haematuria (3.5%) and blood transfusion (0.9%), with lower rates yielded in need for interventions (0.6%) such as catheter insertion for bladder obstruction (0.3%) and nephrectomy (0.01%) and death (0.02%) [49].

The bleeding risk increases in females, use of larger needle (14-G), elevated serum creatinine (>176 umol/L) or acute renal failure, uncontrolled systolic blood pressure (>170 mmHg) [49, 50] and in patients with coagulopathies or are on anticoagulation/antiplatelet agents. Most serious complications are detected within 4 hours of biopsy, and majority within 12 hours [51, 52]. Routine 1-hour post biopsy ultrasound for presence of haematoma to predict complication has not been shown to be clinically beneficial (positive predictive value of 43%; negative predictive value of 95%) [53].


**39**

*Lupus Nephritis: Current Updates*

in treatment withdrawal.

**4.2 Classification criteria**

each division [58].

*4.2.1 SLE and renal involvement*

renal manifestations (**Table 2**) [59].

**4.3 Diagnosis of lupus nephritis**

*DOI: http://dx.doi.org/10.5772/intechopen.96891*

The role of repeat renal biopsy in LN flares is controversial. In essence, a repeat biopsy is required if it may change management; for example, this is particularly true in a patient with stable renal function who developed sudden deterioration of creatinine associated with active urine sediment. This may reflect the possibility of crescentic glomerulonephritis (GN) that warrants stronger immunosuppression. During LN flare, histological transformation is more likely to occur if the initial histology revealed non-proliferative disease (initial class II); although, many would

Renal biopsy may also be considered to determine disease chronicity in patients

The revised American College of Rheumatology (ACR) 1997 criteria specifies that a patient can be diagnosed with SLE if 4 of 11 criteria are met at any interval of observation (**Table 2**). Renal involvement can be considered if patient developed proteinuria of >0.5/day or appearance of cellular cast (red cells, haemoglobin, granular, tubular or mixed) [57]. The 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria divided SLE features into 11 clinical and 6 immunologic criteria, where SLE can be fulfilled by a) biopsy-proven LN in presence of ANA or anti-DNA antibodies or b) meeting ≥4 of 17 criteria, with at least 1 criterion from

European League Against Rheumatism (EULAR)/ACR published a new set of criteria for SLE diagnosis in 2019 [58]. It employs the strategy that ANA must be positive for the diagnosis to be considered, followed by 10 domains with different individual weightage; diagnosis can be made if total score reaches 10 points, again with renal involvement carrying a high weight between 4 and 10 depending on the

The clinical presentations of LN may differ ranging from asymptomatic haematuria to rapidly progressive GN. All patients with SLE should have urinalysis checked on regular basis to detect renal involvement. Presence of significant proteinuria would trigger the need for a renal biopsy, although many would perform biopsies for reasons such as persistent haematuria and elevated serum creatinine [54]. Biopsy is critical to distinguish between active nephritis, non-glomerular pathology of SLE (such as tubulointerstitial nephritis or thrombotic microangiopathy) and disease chronicity (such as interstitial fibrosis, tubular atrophy and

with persistent proteinuria and lower glomerular filtration rate (GFR), which warrant de-escalation of immunosuppression. It is well documented that repeat biopsies lead to change to immunosuppression in more than half of the cases [55]. Decision to stop maintenance immunosuppression in LN is often challenging and some researchers perform 'protocol biopsies' after a period of complete clinical remission to guide withdrawal of treatment. Its' value however is still debatable, as studies mostly looked at the prognosis based on the histological features [54]. In a study by *De Rosa et al.*, 36 LN patients on immunosuppressive therapy for more than 3 years and in clinical remission (proteinuria <0.5 g/day) were re-biopsied. Regardless of the results of biopsy, the immunosuppressive medications were tapered down. Those patients with residual activity in histology had higher chance of relapses upon reducing therapy [56], which supports histology-based approach

still have persistent active lesions in proliferative disease [54, 55].

### **Table 1.**

*Possible indications for kidney biopsy in SLE patient.*

#### *Lupus Nephritis: Current Updates DOI: http://dx.doi.org/10.5772/intechopen.96891*

*Lupus - Need to Know*

clinical practice [45].

class V LN [46].

(0.02%) [49].

value of 95%) [53].

Severe relapse

Proteinuria >0.5 g/24 hours Unexplained renal insufficiency Differentiating activity vs. chronicity

*Possible indications for kidney biopsy in SLE patient.*

**4.1 Role of renal biopsy**

mainstay of current management in LN.

as therapeutic target in LN; unfortunately, none so far had been utilised in daily

In patients suspected of LN, certain clinical and laboratory features may however predict the class of LN a patient may have. In a retrospective study analysing 297 renal biopsies of SLE patients with some degree of proteinuria, absence of malar rash, negative anti-dsDNA and urine leukocytes of <5/high power field under microscopy are independent predictors for class II LN. Class III or IV can independently be predicted by younger age at diagnosis (<32 years), musculoskeletal involvement, hypertension, presence of anti-dsDNA, elevated creatinine level, absence of nephrotic range proteinuria and presence of leucocytes and cellular cast in urine. Older age, malar rash and low C3 level may be predictive for

Renal biopsy is the gold standard for the diagnosis and current classification of LN. The histological findings may assist physicians to optimise therapeutic strategies in individual patients, including assessing disease activity and/or chronicity for guidance to escalate or de-escalate immunosuppression accordingly. It is an invasive procedure with potential risks, most notably bleeding; however, given the lack of available biomarkers to identify disease activity, it remains an irreplaceable tool and

Indication for a renal biopsy includes significant proteinuria of >0.5 g/day (or equivalent), certain unclear acute elevation of serum creatinine level, and in patients with severe disease relapse (**Table 1**) [47]. Biopsy is rarely done in patients with isolated haematuria or proteinuria of <0.5 g/day; hence, class I LN is rarely seen in the histology. Performed by either experienced nephrologist or interven-

Given the location of kidney where no direct compression can be performed post biopsy, bleeding (as detected by routine CT scan or ultrasound post biopsy) was found to be common, ranging in 57–91% of patients [48]; however, the actual incidence of clinically important bleeding is small. Meta-analysis of 34 relevant studies found low rates of macroscopic haematuria (3.5%) and blood transfusion (0.9%), with lower rates yielded in need for interventions (0.6%) such as catheter insertion for bladder obstruction (0.3%) and nephrectomy (0.01%) and death

The bleeding risk increases in females, use of larger needle (14-G), elevated serum creatinine (>176 umol/L) or acute renal failure, uncontrolled systolic blood pressure (>170 mmHg) [49, 50] and in patients with coagulopathies or are on anticoagulation/antiplatelet agents. Most serious complications are detected within 4 hours of biopsy, and majority within 12 hours [51, 52]. Routine 1-hour post biopsy ultrasound for presence of haematoma to predict complication has not been shown to be clinically beneficial (positive predictive value of 43%; negative predictive

> Isolated haematuria or pyuria Proteinuria less than 0.5 g/24 hours 'Protocol' biopsy during/after treatment

Mild relapse

tional radiologist, adequate tissue is obtained in >95% of times.

**Should biopsy May biopsy**

**38**

**Table 1.**

The role of repeat renal biopsy in LN flares is controversial. In essence, a repeat biopsy is required if it may change management; for example, this is particularly true in a patient with stable renal function who developed sudden deterioration of creatinine associated with active urine sediment. This may reflect the possibility of crescentic glomerulonephritis (GN) that warrants stronger immunosuppression. During LN flare, histological transformation is more likely to occur if the initial histology revealed non-proliferative disease (initial class II); although, many would still have persistent active lesions in proliferative disease [54, 55].

Renal biopsy may also be considered to determine disease chronicity in patients with persistent proteinuria and lower glomerular filtration rate (GFR), which warrant de-escalation of immunosuppression. It is well documented that repeat biopsies lead to change to immunosuppression in more than half of the cases [55].

Decision to stop maintenance immunosuppression in LN is often challenging and some researchers perform 'protocol biopsies' after a period of complete clinical remission to guide withdrawal of treatment. Its' value however is still debatable, as studies mostly looked at the prognosis based on the histological features [54]. In a study by *De Rosa et al.*, 36 LN patients on immunosuppressive therapy for more than 3 years and in clinical remission (proteinuria <0.5 g/day) were re-biopsied. Regardless of the results of biopsy, the immunosuppressive medications were tapered down. Those patients with residual activity in histology had higher chance of relapses upon reducing therapy [56], which supports histology-based approach in treatment withdrawal.
