Little et al. first reported the syndrome of loin pain and hematuria in 1967, with the etiology related to disease of peripheral renal arteries. The procedures most often used in this disorder include intraureteric capsaicin, renal denervation or renal autotransplantation. The technique of renal autotransplantation was first performed in 1902 by Emerich (Imre) on canines in Vienna . In recent years laparoscopic approaches have allowed for the possibility of the removal and transplantation of the kidney for loin pain hematuria syndrome (LPHS) through the same incision .
The existence of this syndrome as a distinct pathological entity has been challenged due to the often-observed psychological underpinnings of the condition . However, there are no double blind controlled studies of pain management in this disorder, and no large systematic psychiatric studies of this condition. Some have suggested the disorder to be psychogenic in nature . Designating LPHS as a syndrome has also been challenged, as there is no uniformity in clinical features and outcomes generally seen in a syndrome. Patients described thus far have been predominantly young, white and female, though cases of males with LPHS have been reported [6,7].
Etiology of loin pain hematuria syndrome
Features described with LPHS include severe chronic pain in one or both kidneys, sometimes associated with gross or microhematuria, with variable clinical presentation. There may be benign renal pathology or no identifiable pathology noted in the kidneys. LPHS has been thought to be associated with thin glomerular basement membrane disease with hemorrhage into the renal tubules with swelling of the kidney and pain from distention of the renal capsule .
Numerous other abnormalities have been postulated as being related to LPHS. Although Naish et al. postulated C3 deposition as a factor in LPHS, this is not universally seen, and an estimate of the frequency of this finding in all renal biopsies is around 60% per Kincaid-Smith at University of Melbourne [10–22] (Table 1).
Differential diagnosis of loin pain hematuria syndrome
Many diseases can present with hematuria and loin pain, most notably cancers, including metastatic choriocarcinoma of the kidney , an occult rectal adenocarcinoma causing a urinoma by obstructing ureteral outflow , renal angiomyolipoma , 47 cases of kidney cancer , ovarian cancer , and anaplastic T-cell lymphoma with unilateral upper tract obstruction . Other cases cited in the literature presenting with loin pain and hematuria include a 47-year-old male farmer from Australia with a giant kidney worm (Dioctophyma renale) , one case of polyarteritis nodosa limited to the kidney , a case of renal artery dissection  and a case of a large renal artery aneurysm with resistant hypertension, and heart failure . A medical work-up is needed in all cases of loin pain and hematuria. The diagnosis of somatoform disorder is one of exclusion.
Treatment of loin pain hematuria syndrome
As LPHS is a rare condition, there is no universal standard of care. Generally, the approach is to move from conservative therapies such as ACE inhibitors, chronic pain management program and psychiatric evaluation, to more invasive treatments such as intraureteric capsaicin, renal denervation, and as a last resort renal autotransplantation, renal nephrectomy and dialysis.
Treatment of LPHS:
- Ace inhibitors
- Estrogen withdrawal
- Intraureteric capsaicin
- Kidney pedicle denervation
- Major tranquilizers
- Nerve blocks
- Transcutaneous nerve stimulation
- Ureteral reimplantation
A comparison of the three main strategies for treatment of LPHS shows striking differences in the success rates. Meta-analysis of the three series published using intra ureteral capsaicin revealed an overall rate of pain relief of 57.5%, though from the publications the duration of pain relief could not be determined. Complications of capsaicin treatment included one case of a fibrotic stricture at the pelvic–ureteric junction requiring pyelocystoplasty, one case of ureteric inflammation requiring stenting, one case of mucosal ulceration, and three nephrectomies for nonfunctioning kidneys. The conclusion is that the procedure may be somewhat effective in providing short-medium term symptomatic relief, but is not well tolerated due to a high rate of subsequent renal nonfunction in 7.5% (3/40 patients) [33,34].
Meta-analysis of the two studies published showed that denervation resulted in 25.4% cure rate; three quarters had recurrent pain. Hutchison et al. have postulated that recurrence of pain after splanchnic nerve blockade or renal denervation is due to reinnervation. Autonomic reinnervation has also been observed within 4 weeks of human kidney transplantation reaching the interlobular arteries by 8 months.
Aber and Higgins  first performed renal autotransplantation in England in 1982. Meta-analysis of treatment of LPHS with autotransplantation from available data revealed that 62.5% (45/72) were pain free for more than 1 year, with follow-up from 12–138 months. The total number of subsequent nephrectomies was 8/72 = 11.1%, only one from thrombosis, the others for pain relief. One male patient had bilateral nephrectomies, followed by cadaveric renal transplantation. This patient was pain free at 4 years, though had microhematuria . This approach had been suggested in 1994 by Gibson et al.. The success of autotransplantation in LPHS may be overestimated, as negative studies are less likely to be published [33,34,38–49]Tables 2–4.
Psychological aspects of loin pain hematuria syndrome
As LPHS is considered a rare disease, and less than 500 cases have been reported in the medical literature, a multifactorial biopsychosocial model has not yet been effectively applied to this condition. Even the use of the word syndrome has been controversial as this implies a degree of uniformity in clinical feature and outcome in these cases that may not exist . Since nearly 100 LPHS patients have been reported from one state, Ohio, and the other cases are mainly in the predominantly English speaking countries such as United Kingdom, Australia and Canada it might be tempting to label this a culture-bound syndrome [50••]. One physician from Montreal, Canada stated that he had not seen one case of LPHS in 10 years there, and brought the diagnosis into question. Taguchi [51•] recalled the use of nephropexy in the 1960s; the surgical fixation of the kidney to the psoas muscle to eliminate kinking of the ureter resulting in colicky pain called Dietl's crisis. Both the diagnosis and the procedure are relegated to medical lore. Taguchi questioned whether LPHS is medical diagnosis or fad, and wondered how to distinguish whether the benefit of any surgical procedure is equivalent to a sham surgery. Despite the prevalence of LPHS in English speaking countries, Ghanem has reported on 190 cases of LPHS in Saudi Arabia . Others have stated this is a legitimate medical disorder, and that the psychiatric symptoms are the result rather than the cause of the pain. When underlying pain is addressed the patients quickly wean themselves off narcotics [39,42].
One study compared 15 LPHS patients with 10 patients with complicated kidney stone disease. The patients with LPHS were much more likely to have had parents with serious illness and disability during childhood (P < 0.001), had a greater sense of responsibility for parental illness or distress (P < 0.05) and scored significantly higher on the parental care dimension of the parental bonding instrument (P < 0.05). LPHS patients had significantly less anger and hostility (P < 0.002). The LPHS subjects had three times as many MUPS (medically unexplained physical symptoms) as the control subjects (P < 0.01), and more regular analgesic use (P < 0.01). There was no difference in current rates of anxiety or depression between the 2 groups, but pain onset in the LPHS patients was significantly more likely to coincide with some psychological event (P < 0.02) than the kidney stone patients. The authors concluded that LPHS patients might have a somatoform pain disorder [53••]. The small size raises the question of whether this was a representative sampling of LPHS patients. The other question is whether this group of LPHS patients represents the result of sampling error due to biased referral from nephrologists or urologists. For example, in spastic dysphonia, the typical patient seen by the pulmonary physician differs from the subgroup referred to psychiatrists. Overall, Factitious disorder (Munchausen's syndrome) and malingering have been reported in very few patients in the medical literature on LPHS [39,42,54,55]. If the majority of patients with LPHS had a somatoform pain disorder would surgical interventions such as autotransplantation still be considered ethical? Generally, surgery is considered only as a last resort. However, as there are no published cases of successful psychiatric treatment of LPHS, and a high rate of opiate addiction and total disability, even if surgical procedures were sham procedures, would this be ethical? Along those lines, if capsaicin treatment, renal denervation and renal autotransplantation were all sham procedures then why would the success rate of these procedures differ? Theoretically, the success rates of various placebo treatments for LPHS should be equally effective. Perhaps the diversity of diagnoses under the rubric of LPHS accounts for the varying success. Francis has suggested that the denervation technique makes a difference, especially if only the renal artery and vein are divided and the innervation to the ureter remains . Possibly patient perception of the three treatments differs. The prospect of having something akin to hot pepper juice in an alcohol solution flushed through the ureters and bladder may be viewed as more drastic than renal denervation under anesthesia. Perhaps any type of transplant carries a sort of halo effect, because reinnervation has been observed after both transplant and renal denervation procedures, yet autotransplant is the more successful procedure for LPHS. Autotransplantation is dramatic and would make for fine storytelling for years afterwards if Munchausen's syndrome was the underlying disorder. If the etiology of LPHS were ultimately found to be psychological, would the success with autotransplantation decrease? The answer is unknown, but there are other psychological disorders that respond to surgical interventions, such as cingulotomy for OCD.
An ethical analysis of autotransplantation for loin pain hematuria syndrome
Any ethical analysis of autotransplantation in LPHS must weigh the risks and benefits of the three main procedures generally done, potential harm to the patient, and more conservative alternatives as well as the consequences of doing nothing. In these cases, the consequences of doing nothing are generally opiate addiction and total disability. However, one patient remained employed and functional through a stepped intervention approach over 18 years leading to parenteral opiates through a Hickman line . In another case an intrathecal implantable morphine pump was effective .
There are several ethical arguments in favor of autotransplantation. The first argument is that autotransplantation is offers the best chance for long lasting pain relief with the highest likelihood of retaining renal function. The patient's right to autonomy is the crux of the matter; to do as they please with their own organs in an effort to gain relief from chronic suffering and return to gainful employment. An evaluation of the patient's capacity to make sound medical decisions is essential in LPHS.
From the physician's standpoint, a utilitarian approach would be favored to maximize the well being of the majority of patients with LPHS. The concept of beneficence could be invoked also with the goal of relieving suffering, decreasing unemployment and financial hardship, and eliminating or decreasing opiate dependence.
Arguments against autotransplantation in LPHS center on the concept of nonmaleficence, from the physician's Hippocratic oath, ‘first do no harm’. Another argument is to respect the sanctity of the body, and not allow the patient to engage in self-harm, especially if one believes this disorder to be essentially a psychological disorder. The idea of treating a psychological disorder with a surgical procedure is repugnant to many, but has been done in other areas such as cingulotomy for severe unremitting OCD, and with deep brain stimulation for severe mood disorders. The harm to third parties (societal harms) involve time off from work for the caregiver caring for the patient postoperatively, health insurance costs to pay for the procedure, and short-term disability insurance costs postoperatively during recuperation. There is a risk that an autotransplant participant may need dialysis or renal transplant if nonfunction results from the autotransplant. The risk of death in autotranplant is probably similar to the risk of death in cadaveric or live donor renal transplantation, around 0.02%.
Loin pain hematuria syndrome is a controversial diagnosis. However, whether this condition exists as a discrete entity or a collection of disparate disorders under the rubric LPHS remains to be elucidated. Although rare, this condition is becoming more widely appreciated. In addition to the usual medical work-up, gathering data from a psychiatric standpoint may answer the question of what percentage of these patients meet criteria for somatoform pain disorder. Utilizing standardized psychological instruments may be helpful to tease out the psychiatric components of this disorder. Gathering additional data about MUPS (medically unexplained medical symptoms) and probing to determine whether pain onset correlates with psychological event be useful in making the diagnosis of somatoform pain disorder. Administering a depression and an anxiety rating scale may confirm whether there are significant symptoms to target with antidepressant medications or anxiolytics.
Guidelines for a systematic biopsychosocial approach to study of this disorder may help provide a framework for a medical evidence-based treatment approach in these challenging patients in the future as well as a means for tracking long-term outcomes.
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 000–000).
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Loin pain-hematuria syndrome. 2008; www.uptodate.com
This is a provocative overview of clinical feature and treatment of LPHS.
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