Renal Complications in Henoch-Schönlein Purpura

First described in 1837, Henoch-Schönlein purpura (HSP) is an IgA-mediated small vessel vasculitis distinguished by the clinical tetrad of palpable purpura, abdominal pain, arthritis and kidney disease termed HSP nephritis.

Of childhood vasculitides, HSP carries the greatest risk for acute then chronic progressive kidney dysfunction from immunologic injury to glomerular structures. Understanding the patterns of inflammation and associated markers like proteinuria guides treatment and monitoring.

Pathogenesis of Kidney Involvement in HSP

The inciting triggers provoking systemic HSP remain unclear. However, the downstream pathway targeting the kidneys likely involves:

Generation of Aberrantly Glycosylated IgA

Multiple infections and toxins are postulated to initiate abnormal synthesis of the immunoglobulin A (IgA) antibody subclass, yielding varieties deficient in galactose molecules on their hinges.

IgA Immune Complex Formation and Deposition

These poorly glycosylated IgA antibodies resist normal clearance, so form complexes that deposit along glomerular capillary walls in the kidney and other vascular beds.

Inflammatory Cascade Activation

The planted immune complexes then activate inflammatory pathways involving cytokines, complement proteins, platelet aggregation signals, and leukocyte migration. These effect tissue swelling, cell proliferation, enzyme release degrading structures, and disrupted barriers.

Proteinuria Ensues

Disruption of the filtration barrier allows blood proteins like albumin to leak into the urine as the most common manifestation of HSP nephritis. Hematuria from damaged vessels frequently accompanies protein loss.

Without treatment, cycles of repair and re-injury remodel glomeruli into non-functional scar tissue no longer filtering properly.

Patterns of Kidney Involvement in HSP

Reported frequencies of nephritis complicating HSP vary widely from 20-80% across cohorts. Yet despite similar acute onset courses clinically, diverse glomerular outcomes emerge over time:

Self-Limited Acute Glomerulonephritis

The most common pattern in children is resolution of minor proteinuria and microscopic hematuria along with other HSP symptoms within 4-6 weeks. Serology normalizes without permanent loss of filtration capacity.

Spontaneously Resolving Relapses

A subset suffer recurring flares of evident blood with or without hypertension over months, controlled by brief steroids without cumulative damage.

Rapidly Progressive Glomerulonephritis

Rarely, some patients rapidly develop heavy proteinuria with red cell casts, hypertension and rising serum creatinine marking severe crescents obliterating glomeruli.

Chronic Kidney Disease

Despite multiple interventions, immunologic flares culminating in fibrosis silently replace nephrons over months to years until manifestation as hypertension, uremia and edema emerges.

Understanding individual risk profiles and trajectories guides treatment of the variable HSP kidney manifestations.

Risk Factors for Renal Progression in HSP

Multiple cohort analyses have aimed to define clinical and histologic features predictive of destructive rather than healed outcomes. Consistent patterns include:

Young Age

Onset under age 6 years independently predicts renal involvement in HSP. Immature immunity may incite exaggerated inflammation unresolved by usual mechanisms.

Male Gender

Adjusted for other characteristics, male gender consistently associates with higher nephritis rates around 60% versus 40% in females. The basis remains speculative but affects screening intensity.

Early Markers of Nephritis

Heavy proteinuria, hypertension, or severe glomerular changes early after diagnosis reflect vigorous disease warranting close surveillance and second line medications.

Relapses

Recurrent symptomatic disease flares signal ongoing propensity for kidney redeposit and damage, especially within the initial 6 months. Preventative regimens may benefit frequent relapsers.

Identifying those at highest risk for deterioration guarantees timely intervention while lesions remain responsive to immunotherapy.

The Role of Proteinuria as a Marker of HSP Kidney Involvement

The cardinal manifestation of HSP nephritis is blood vessel leakage allowing serum proteins access into the urine, appearing as proteinuria on testing. This signals structural derangements permitting large molecular weight molecules like albumin to traverse the filtration barrier unimpeded along pressure gradients.

As foot process effacement and basement membrane disruption disrupt the charge and size selectivity of the glomerular filter, increasing quantities of protein flow into urine as damage accrues. Thus protein excretion proportionately estimates filtration surface area loss overall, making proteinuria a surrogate for sclerotic changes presaging impairment.

Grading Severity of Proteinuria in HSP

Unlike adult primary glomerular disease where thresholds differentiate risk categories, no standardized pediatric schema defines urgent versus concerning levels specifically in HSP nephritis currently. However by analogy to other glomerulonephritis, roughly:

Subnephrotic Proteinuria

Trace to 2+ dipstick or urine protein/creatinine ratio under 2 g/g may accompany most acute cases but taper spontaneously without specific therapy if all else stable. Repeat check in 6-12 weeks.

Nephrotic-Range Proteinuria

Massive protein leakage over 50 mg/m2/hr or clinical manifestations like edema signals extensive glomerular inflammation unlikely to resolve spontaneously. Indicates likely progression without augmented treatment.

Fixed Proteinuria

Persisting heavy proteinuria despite therapy over 0.5-1 g/day extrapolates substantial immutable filtration surface loss translating to higher long term kidney detriment.

Notably proteinuria at onset associated with poor histologic features presages resistance to treatment and represents the strongest predictor of renal survival long term.

Using Proteinuria to Guide HSP Treatment Intensity

Customizing regimens based on quantified protein loss balances under and overtreatment for this condition with fluctuating courses:

Mild Proteinuria

Isolated microscopic hematuria orProtein less than 0.5 g/day may only warrant renin angiotensin system blockade and blood pressure optimization as needed without intensive immunosuppression potentially avoiding side effects.

Heavy Proteinuria

Over 1 gram daily protein leak indicates uncontrolled immunologic attack requiring escalation to steroids plus adjuvant agents like cyclophosphamide to directly reduce inflammation and secondary fibrosis. Timingaround 6 months proves critical.

Monitoring Interval Adjustments

The higher the proteinuria, the closer the follow up interval should be to promptly recognize resistance or relapse warranting further increases. Monthly urine checks when over 500 mg daily ensures minor deterioration is not missed.

Preserved Function Prioritization

If filtration capacity remains stable, the goal becomes reducing proteinuria to subnephrotic levels to improve long term projections after the acute damage subsides, even if not eliminated fully. Preventing further loss is paramount.

Thus protein quantification indexes both injury activity and efficacy response, fine tuning therapeutic modifications defending renal viability in HSP nephritis.

Long Term Implications of Persistent Proteinuria After HSP

Unlike self-limited syndromes, HSP nephritis carries risk for insidiously progressive glomerular failure either steadily or in fits and starts after acute resolution through mechanisms outlined earlier. Cases series analysis reveals adverse outcomes correlate with unfavorable baseline features:

Proteinuria Chronicity

Persistent protein leakage despite immunotherapy beyond 6-12 months associates with treatment resistance portending antigen/antibody persistence driving fibrosis. Early protein suppression is paramount.

Nephrotic Range Proteinuria

Massive uncontrolled protein spill communicates both relentless insult and filtration incompetence unlikely to recover. Without immune stalemate, sclerosis culminates in end stage kidney disease over variable intervals.

Hypertension

While often transient initially, elevated blood pressure proving refractory to multi-drug regimens indirectly signals tissue remodeling limiting vascular compliance and kidney reserve. Pressure ambits forecast course.

Thus while HSP nephritis cannot be considered benign short term given potential for fulminant crescentic decline, close longitudinal tracking of proteinuria indexes insidious progression risks long after the early dramatic symptoms wane.

FAQs About Proteinuria in HSP

Below are answers to frequently asked questions regarding proteinuria in Henoch-Schönlein purpura nephritis:

Is any proteinuria level safe to ignore in HSP?

No, all grades deserve repeat quantification and clinical correlation, as early leaks predict relapse and incremental loss risks. Care must be taken not to overlook bland urinary dipstick traces that normalize but later recur relentlessly as immunologic flares. What appears static may presage progressive damage in disguise.

Does fixing heavy proteinuria in HSP restore long term prognosis?

Unfortunately not always. As with most glomerular diseases, if nephrons aresilenced by longstanding inflammation and fibrosis despite eventual protein suppression, hypertension and decline may slowly emerge as remaining units erode from hyperfiltration stresses over years of compensatory adaptations unseen.

Is specific therapy warranted for lower grade proteinuria under 500 mg daily?

Opinion evolves on this issue balancing benefits and toxicity. For persistent low grade leakage, renin angiotensin blockade and low dose alternate day prednisone likely still improve projections more than monitoring alone by directly reducing intraglomerular pressures and inflammation respectively without intensive toxicity.

How often should urine protein levels be rechecked after an acute HSP episode?

Guidelines endorse urine studies every 3 months for the first year, then at least twice yearly indefinitely after any HSP nephritis, given the tendency for silent recurrences triggering incremental damage. More concerning baseline levels warrant monthly quantification initially.

What precautions help preserve kidney health when HSP nephritis risk is present?

Preventing modifiable impairment when fibrosis risk persists involves strict blood pressure targets under 120/80 using multipharmacology, dietary sodium restriction, smoking cessation, avoidance of nephrotoxic substances, and judicious hydration without overdiuresis.

Conclusion and Takeaway Points

In summary, key aspects regarding proteinuria in HSP:

• Quantified urinary protein correlates with severity of glomerular inflammation and long term prognosis.
• Heavy loss signals need for augmented treatment to prevent amyloid nephron demise.
• Some leakage may persist subtly before recurring or slowly progressing.
• Therefore, vigilant monitoring of proteinuria in HSP nephritis remains essential for optimizing eventual function and survival.

Integrating clinical status with protein measurement trajectory personalizes treatment intensity to stabilize overall projections in Henoch Schönlein purpura complicated by immunologic renal involvement.

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